1,721,070 research outputs found
Taurine Supplementation Restores Insulin Secretion And Reduces Er Stress Markers In Protein-malnourished Mice
No full textEndoplasmic reticulum (ER) stress is a cellular response to increased intra-reticular protein accumulation or poor ER function. Chronic activation of this pathway may lead to beta cell death and metabolic syndrome (MS). Poor nutrition during perinatal period, especially protein malnutrition, is associated with increased risk for MS in later life. Here, we analyzed the effects of taurine (TAU) supplementation upon insulin secretion and ER stress marker expression in pancreatic islets and in the liver from mice fed a low-protein diet. Malnourished mice had lower body weight and plasma insulin. Their islets secreted less insulin in response to stimulatory concentrations of glucose. TAU supplementation increased insulin secretion in both normal protein and malnourished mice. Western blot analysis revealed lower expression of the ER stress markers CHOP and ATF4 and increased phosphorylation of the survival protein Akt in pancreatic islets of TAU-supplemented mice. The phosphorylation of the mitogenic protein extracellular signal-regulated kinase (ERK1/2) was increased after acute incubation with TAU. Finally, the ER stress markers p-PERK and BIP were increased in the liver of malnourished mice and TAU supplementation normalized these parameters. In conclusion, malnutrition leads to impaired islet function which is restored with TAU supplementation possibly by increasing survival signals and lowering ER stress proteins. Lower ER stress markers in the liver may also contribute to the improvement of insulin action on peripheral organs. © Springer Science+Business Media New York 2013.776129139Amaral, A.G., Rafacho, A., Machado De Oliveira, C.A., Batista, T.M., Ribeiro, R.A., Latorraca, M.Q., Boschero, A.C., Carneiro, E.M., Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice (2010) Pancreas, 39, pp. 847-855Batista, T.M., Ribeiro, R.A., Amaral, A.G., De Oliveira, C.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation restores glucose and carbachol-induced insulin secretion in islets from lowprotein diet rats: Involvement of Ach-M3R, Synt 1 and SNAP-25 proteins (2012) J Nutr Biochem, 23, pp. 306-312Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Carneiro, E.M., Latorraca, M.Q., Araujo, E., Beltra, M., Oliveras, M.J., Navarro, M., Berna, G., Martin, F., Taurine supplementation modulates glucose homeostasis and islet function (2009) J Nutr Biochem, 20, pp. 503-511Chen, J.H., Martin-Gronert, M.S., Tarry-Adkins, J., Ozanne, S.E., Maternal protein restriction affects postnatal growth and the expression of key proteins involved in lifespan regulation in mice (2009) PLoS One, 4, pp. e4950Cherif, H., Reusens, B., Ahn, M.T., Hoet, J.J., Remacle, C., Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet (1998) J Endocrinol, 159, pp. 341-348Cnop, M., Foufelle, F., Velloso, L.A., Endoplasmic reticulum stress, obesity and diabetes (2012) Trends Mol Med, 18, pp. 59-68Da Silva, P.M., Batista, T.M., Ribeiro, R.A., Zoppi, C.C., Boschero, A.C., Carneiro, E.M., Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: Effect of leucine supplementation (2012) Metabolism, 61, pp. 721-732Eizirik, D.L., Cardozo, A.K., Cnop, M., The role for endoplasmic reticulum stress in diabetes mellitus (2008) Endocr Rev, 29, pp. 42-61Filiputti, E., Ferreira, F., Souza, K.L., Stoppiglia, L.F., Arantes, V.C., Boschero, A.C., Carneiro, E.M., Impaired insulin secretion and decreased expression of the nutritionally responsive ribosomal kinase protein S6K-1 in pancreatic islets from malnourished rats (2008) Life Sci, 82, pp. 542-548Filiputti, E., Rafacho, A., Araujo, E.P., Silveira, L.R., Trevisan, A., Batista, T.M., Curi, R., Carneiro, E.M., Augmentation of insulin secretion by leucine supplementation in malnourished rats: Possible involvement of the phosphatidylinositol 3-phosphate kinase/mammalian target protein of rapamycin pathway (2010) Metabolism, 59, pp. 635-644Gentile, C.L., Nivala, A.M., Gonzales, J.C., Pfaffenbach, K.T., Wang, D., Wei, Y., Jiang, H., Maclean, K.N., Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease (2011) Am J Physiol Regul Integr Comp Physiol, 301, pp. R1710-R1722Hales, C.N., Barker, D.J., Type 2 (non-insulin-dependent) diabetes mellitus: The thrifty phenotype hypothesis (1992) Diabetologia, 35, pp. 595-601Hotamisligil, G.S., Endoplasmic reticulum stress and the inflammatory basis of metabolic disease (2010) Cell, 140, pp. 900-917Jaquet, D., Gaboriau, A., Czernichow, P., Levy-Marchal, C., Insulin resistance early in adulthood in subjects born with intrauterine growth retardation (2000) J Clin Endocrinol Metab, 85, pp. 1401-1406Lin, J.H., Walter, P., Yen, T.S., Endoplasmic reticulum stress in disease pathogenesis (2008) Annu Rev Pathol, 3, pp. 399-425Lytton, J., Westlin, M., Hanley, M.R., Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps (1991) J Biol Chem, 266, pp. 17067-17071Maturo, J., Kulakowski, E.C., Taurine binding to the purified insulin receptor (1988) Biochem Pharmacol, 37, pp. 3755-3760Nakaya, Y., Minami, A., Harada, N., Sakamoto, S., Niwa, Y., Ohnaka, M., Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes (2000) Am J Clin Nutr, 71, pp. 54-58Ozanne, S.E., Dorling, M.W., Wang, C.L., Nave, B.T., Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats (2001) Am J Physiol Endocrinol Metab, 280, pp. E534-E539Ozcan, U., Cao, Q., Yilmaz, E., Lee, A.H., Iwakoshi, N.N., Ozdelen, E., Tuncman, G., Hotamisligil, G.S., Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes (2004) Science, 306, pp. 457-461Pan, C., Prentice, H., Price, A.L., Wu, J.Y., Beneficial effect of taurine on hypoxia- and glutamateinduced endoplasmic reticulum stress pathways in primary neuronal culture (2012) Amino Acids, 43 (2), pp. 845-855Petry, C.J., Dorling, M.W., Pawlak, D.B., Ozanne, S.E., Hales, C.N., Diabetes in old male offspring of rat dams fed a reduced protein diet (2001) Int J Exp Diabetes Res, 2, pp. 139-143Reis, M.A., Carneiro, E.M., Mello, M.A., Boschero, A.C., Saad, M.J., Velloso, L.A., Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats (1997) J Nutr, 127, pp. 403-410Remacle, C., Dumortier, O., Bol, V., Goosse, K., Romanus, P., Theys, N., Bouckenooghe, T., Reusens, B., Intrauterine programming of the endocrine pancreas (2007) Diabetes Obes Metab, 9 (SUPPL. 2), pp. 196-209Ribeiro, R.A., Bonfleur, M.L., Amaral, A.G., Vanzela, E.C., Rocco, S.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets (2009) Diabetes Metab Res Rev, 25, pp. 370-379Ribeiro, R.A., Santos-Silva, J.C., Vettorazzi, J.F., Cotrim, B.B., Mobiolli, D.D., Boschero, A.C., Carneiro, E.M., Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic beta-cells (2012) Amino Acids, 43 (4), pp. 1791-1801Ribeiro, R.A., Vanzela, E.C., Oliveira, C.A., Bonfleur, M.L., Boschero, A.C., Carneiro, E.M., Taurine supplementation: Involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2+ handling in mouse pancreatic islets (2010) Br J Nutr, 104, pp. 1148-1155Sparre, T., Reusens, B., Cherif, H., Larsen, M.R., Roepstorff, P., Fey, S.J., Mose Larsen, P., Nerup, J., Intrauterine programming offetal islet gene expression in rats-effects of maternal protein restriction during gestation revealed by proteome analysis (2003) Diabetologia, 46, pp. 1497-1511Theys, N., Bouckenooghe, T., Ahn, M.T., Remacle, C., Reusens, B., Maternal low-protein diet alters pancreatic islet mitochondrial function in a sex-specific manner in the adult rat (2009) Am J Physiol Regul Integr Comp Physiol, 297, pp. R1516-R1525Tsuboyama-Kasaoka, N., Shozawa, C., Sano, K., Kamei, Y., Kasaoka, S., Hosokawa, Y., Ezaki, O., Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity (2006) Endocrinology, 147, pp. 3276-3284Vo, T., Hardy, D.B., Molecular mechanisms underlying the fetal programming of adult disease (2012) J Cell Commun Signal, 43 (4), pp. 1791-1801Zhang, Y., Xia, Z., La Cour, K.H., Ren, J., Activation of Akt rescues endoplasmic reticulum stress-impaired murine cardiac contractile function via glycogen synthase kinase-3beta-mediated suppression of mitochondrial permeation pore opening (2011) Antioxid Redox Signal, 15, pp. 2407-2424Zhou, Y., Lee, J., Reno, C.M., Sun, C., Park, S.W., Chung, J., Lee, J., Ozcan, U., Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction (2011) Nat Med, 17, pp. 356-36
Morphofunctional Alterations In Endocrine Pancreas Of Short- And Long-term Dexamethasone-treated Rats
No full textLong-term dexamethasone therapy may induce peripheral insulin resistance (IR), which in turn elicits increased beta-cell function and proliferation. However, whether such adaptive compensations occur during short-term treatment with dexamethasone is unclear. Here, we compared morphofunctional parameters in endocrine pancreas after short- and long-term dexamethasone administration. Groups of rats received daily i. p. injection of 1 mg/kg b. w. dexamethasone for 1 (DEX-1), 3 (DEX-3), or 5 consecutive days (DEX-5), whilst control rats were saline-treated (CTL). Despite the absence of apparent IR in DEX-1 rats, this group exhibited increased circulating insulin levels and glucose-stimulated insulin secretion (GSIS), compared to the CTL group (p<0.05). Evident IR as well as marked hyperinsulinemia and GSIS, as judged by the static and dynamic insulin secretion values, were observed in DEX-3 and DEX-5 rats (p<0.05). GSIS in islets cultured with 1 M dexamethasone was lower compared to the control (p<0.05). Marked increases in beta-cell proliferation were observed in DEX-3 and DEX-5 rats, compared to CTL and DEX-1 rats (p<0.05). The alterations observed in DEX-3 rats were more pronounced in DEX-5 rats, which also exhibited a higher content of islet Cdk4 and Cd2 proteins, compared to the CTL group (p<0.05). We conclude that short-term dexamethasone treatment (DEX-1) induces an increase in beta-cell function that does not require the presence of discernible IR. As the treatment continues, the IR develops rapidly, and increased insulin secretion as well as beta-cell hyperplasia is demanded for the appropriate maintenance of glucose homeostasis. © Georg Thieme Verlag KG Stuttgart - New York.434275281Schacke, H., Docke, W.-D., Asadullah, K., Mechanisms involved in the side effects of glucocorticoids (2002) Pharmacology and Therapeutics, 96 (1), pp. 23-43. , DOI 10.1016/S0163-7258(02)00297-8, PII S0163725802002978Andrews, R.C., Walker, B.R., Glucocorticoids and insulin resistance: Old hormones, new targets (1999) Clinical Science, 96 (5), pp. 513-523. , DOI 10.1042/CS19980388Kahn, S.E., Prigeon, R.L., McCulloch, D.K., Boyko, E.J., Bergman, R.N., Schwartz, M.W., Neifing, J.L., Porte Jr., D., Quantification of the relationship between insulin sensitivity and β- cell function in human subjects: Evidence for a hyperbolic function (1993) Diabetes, 42 (11), pp. 1663-1672Karlsson, S., Ostlund, B., Myrsen-Axcrona, U., Sundler, F., Ahren, B., Beta cell adaptation to dexamethasone-induced insulin resistance in rats involves increased glucose responsiveness but not glucose effectiveness (2001) Pancreas, 22 (2), pp. 148-156. , DOI 10.1097/00006676-200103000-00007Nicod, N., Giusti, V., Besse, C., Tappy, L., Metabolic adaptations to dexamethasone-induced insulin resistance in healthy volunteers (2003) Obesity Research, 11 (5), pp. 625-631Rafacho, A., Cestari, T.M., Taboga, S.R., Boschero, A.C., Bosqueiro, J.R., High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets (2009) Am J Physiol Endocrinol Metab, 296, pp. E681-E689Rafacho, A., Marroquí, L., Taboga, S.R., Abrantes, J.L., Silveira, L.R., Boschero, A.C., Carneiro, E.M., Quesada, I., Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus-secretion coupling in isolated rat islets (2010) Endocrinology, 151, pp. 85-95Rafacho, A., Giozzet, V.A.G., Boschero, A.C., Bosqueiro, J.R., Functional alterations in endocrine pancreas of rats with different degrees of dexamethasone-induced insulin resistance (2008) Pancreas, 36 (3), pp. 284-293. , DOI 10.1097/MPA.0b013e31815ba826, PII 0000667620080400000010Rafacho, A., Roma, L.P., Taboga, S.R., Boschero, A.C., Bosqueiro, J.R., Dexamethasone-induced insulin resistance is associated with increased connexin 36 mRNA and protein expression in pancreatic rat islets (2007) Canadian Journal of Physiology and Pharmacology, 85 (5), pp. 536-545. , DOI 10.1139/Y07-037Beith, J.L., Alejandro, E.U., Johnson, J.D., Insulin stimulates primary β-cell proliferation via Raf-1 kinase (2008) Endocrinology, 149 (5), pp. 2251-2260. , http://endo.endojournals.org/cgi/reprint/149/5/2251, DOI 10.1210/en.2007-1557Rafacho, A., Ribeiro, D.L., Boschero, A.C., Taboga, S.R., Bosqueiro, J.R., Increased pancreatic islet mass is accompanied by activation of the insulin receptor substrate-2/serine-threonine kinase pathway and augmented cyclin D 2 protein levels in insulin-resistant rats (2008) International Journal of Experimental Pathology, 89 (4), pp. 264-275. , DOI 10.1111/j.1365-2613.2008.00588.xKawai, A., Kuzuya, N., On the role of glucocorticoid in glucose-induced insulin secretion (1977) Hormone and Metabolic Research, 9 (5), pp. 361-365Burén, J., Lai, Y.C., Lundgren, M., Eriksson, J.W., Jensen, J., Insulin action and signalling in fat and muscle from dexamethasone- treated rats (2008) Arch Biochem Biophys, 474, pp. 91-101Mokuda, O., Sakamoto, Y., Ikeda, T., Mashiba, H., Sensitivity and responsiveness of glucose output to insulin in isolated perfused liver from dexamethasone-treated rats (1991) Horm Metab Res, 23, pp. 53-55Beard, J.C., Halter, J.B., Best, J.D., Dexamethasone-induced insulin resistance enhances B cell responsiveness to glucose level in normal men (1984) American Journal of Physiology - Endocrinology and Metabolism, 10 (5), pp. E592-E596Novelli, M., De Tata, V., Bombara, M., Lorenzini, A., Masini, M., Pollera, M., Bergamini, E., Masiello, P., Insufficient adaptive capability of pancreatic endocrine function in dexamethasone-treated ageing rats (1999) Journal of Endocrinology, 162 (3), pp. 425-432. , DOI 10.1677/joe.0.1620425Sood, A., Ismail-Beigi, F., Effect of dexamethasone on insulin secretion: Examination of some underlying mechanisms (2010) Endocr Pract, 29, pp. 1-24Qi, D., Pulinilkunnil, T., An, D., Ghosh, S., Abrahani, A., Pospisilik, J.A., Brownsey, R., Rodrigues, B., Single-dose dexamethasone induces whole-body insulin resistance and alters both cardiac fatty acid and carbohydrate metabolism (2004) Diabetes, 53 (7), pp. 1790-1797. , DOI 10.2337/diabetes.53.7.1790Zakrzewska, K.E., Cusin, I., Stricker-Krongrad, A., Boss, O., Ricquier, D., Jeanrenaud, B., Rohner-Jeanrenaud, F., Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat (1999) Diabetes, 48 (2), pp. 365-370. , DOI 10.2337/diabetes.48.2.365Angelini, N., Rafacho, A., Boschero, A.C., Bosqueiro, J.R., Involvement of the cholinergic pathway in glucocorticoid-induced hyperinsulinemia in rats (2010) Diabetes Res Clin Pract, 87, pp. 184-191Ahrén, B., Evidences that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans (2008) Diabetologia, 51, pp. 1018-1024Rafacho, A., Quallio, S., Ribeiro, D.L., Taboga, S.R., Paula, F.M., Boschero, A.C., Bosqueiro, J.R., The adaptive compensations in endocrine pancreas from glucocorticoid-treated rats are reversible after the interruption of treatment (2010) Acta Physiol, 200, pp. 223-235Weir, G.C., Laybutt, D.R., Kaneto, H., Bonner-Weir, S., Sharma, A., β-Cell adaptation and decompensation during the progression of diabetes (2001) Diabetes, 50 (SUPPL. 1), pp. S154-S15
Age- And Gender-related Changes In Glucose Homeostasis In Glucocorticoid-treated Rats
No full textThe disruption to glucose homeostasis upon glucocorticoid (GC) treatment in adult male rats has not been fully characterized in older rats or in females. Thus, we evaluated the age- and gender-related changes in glucose homeostasis in GC-treated rats. We injected male and female rats at 3 months and 12 months of age with either dexamethasone (1.0 mg/kg body mass, intraperitoneally) or saline, daily for 5 days. All of the GC-treated rats had decreased body mass and food intake, and adrenal hypotrophy. Increased glycemia was observed in all of the GC-treated groups and only the 3-month-old female rats were not glucose intolerant. Dexamethasone treatment resulted in hyperinsulinemia and hypertriacylglyceridemia in all of the GC-treated rats. The glucose-stimulated insulin secretion (GSIS) was higher in all of the dexamethasone-treated animals, but it was less pronounced in the older animals. The β-cell mass was increased in the younger male rats treated with dexamethasone. We conclude that dexamethasone treatment induces glucose intolerance in both the 3- and 12-month-old male rats as well as hyperinsulinemia and augmented GSIS. Three-month-old female rats are protected from glucose intolerance caused by GC, whereas 12-month-old female rats developed the same complications that were present in 3- and 12-month-old male rats.9210867878Angelini, N., Rafacho, A., Boschero, A.C., Bosqueiro, J.R., Involvement of the cholinergic pathway in glucocorticoid-induced hyperinsulinemia in rats (2010) Diabetes Res. Clin. Pract, 87, pp. 184-191. , PMID:19962776Beard, J.C., Halter, J.B., Best, J.D., Pfeifer, M.A., Porte, D., Jr., Dexamethasone-induced insulin resistance enhances B cell responsiveness to glucose level in normal men (1984) Am. J. Physiol, 247, pp. E592-E596. , PMID: 6388353Binnert, C., Ruchat, S., Nicod, N., Tappy, L., Dexamethasone-induced insulin resistance shows no gender difference in healthy humans (2004) Diabetes Metab, 30, pp. 321-326. , PMID:15525874Caldefie-Chézet, F., Moinard, C., Minet-Quinard, R., Gachon, F., Cynober, L., Vasson, M., Dexamethasone treatment induces long-lasting hyperleptinemia and anorexia in old rats (2001) Metabolism, 50, pp. 1054-1058. , PMID:11555838Caperuto, L.C., Anhê, G.F., Amanso, A.M., Ribeiro, L.M., Medina, M.C., Souza, L.C., Distinct regulation of IRS proteins in adipose tissue from obese aged and dexamethasone-treated rats (2006) Endocrine, 29, pp. 391-398. , PMID:16943575Chimin, P., Farias Toda, S., Torres-Leal, F.L., Bolsoni-Lopes, A., Campaña, A.B., Andreotti, S., Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar rats (2014) Acta Physiol. (Oxf.), 211, pp. 409-420. , PMID:24410866Choi, S.B., Jang, J.S., Hong, S.M., Jun, D.W., Park, S., Exercise and dexamethasone oppositely modulate beta-cell function and survival via independent pathways in 90% pancreatectomized rats (2006) J. Endocrinol, 190, pp. 471-482. , PMID:16899580De Paula, F.M., Boschero, A.C., Carneiro, E.M., Bosqueiro, J.R., Rafacho, A., Insulin signaling proteins in pancreatic islets of insulin-resistant rats induced by glucocorticoid (2011) Biol. Res, 44, pp. 251-257. , PMID:22688912De Toro-Martín, J., Fernández-Millán, E., Lizárraga-Mollinedo, E., López-Oliva, E., Serradas, P., Escrivá, F., (2014) Predominant Role of GIP in the Development of a Metabolic Syndrome-like Phenotype in Female Wistar Rats Submitted to Forced Catch-up Growth. Endocrinology, , In press. PMID:25032669Fink, R.I., Kolterman, O.G., Olefsky, J.M., The physiological significance of the glucose intolerance of aging (1984) J. Gerontol, 39, pp. 273-278. , PMID:6371116Fransson, L., Dos Santos, C., Wolbert, P., Sjöholm, A., Rafacho, A., Ortsäter, H., Liraglutide counteracts obesity and glucose intolerance in a mouse model of glucocorticoid-induced metabolic syndrome (2014) Diabetol. Metab. Syndr, 6, p. 3. , PMID:24423471Frias, J.P., McAraeg, G.B., Ofrecio, J., Yu, J.G., Olefsky, J.M., Kruszynska, Y.T., Decreased susceptibility to fatty acid-induced peripheral tissue insulin resistance in women (2001) Diabetes, 50, pp. 1344-1350. , PMID:11375335Gama, R., Medina-Layachi, N., Ranganath, L., Hampton, S., Marks, V., Hyperproinsulinaemia in elderly subjects: Evidence for age-related pancreatic beta-cell dysfunction (2000) Ann. Clin. Biochem, 37, pp. 367-371. , PMID:10817253Gathercole, L.L., Lavery, G.G., Morgan, S.A., Cooper, M.S., Sinclair, A.J., Tomlinson, J.W., 11β-hydroxysteroid dehydrogenase 1: Translational and therapeutic aspects (2013) Endocr. Rev, 34, pp. 525-555. , PMID:23612224Giozzet, V.A., Rafacho, A., Boschero, A.C., Carneiro, E.M., Bosqueiro, J.R., Dexamethasone treatment in vivo counteracts the functional pancreatic islet alterations caused by malnourishment in rats (2008) Metabolism, 57, pp. 617-624. , PMID:18442623Hevener, A., Reichart, D., Janez, A., Olefsky, J., Female rats do not exhibit free fatty acid-induced insulin resistance (2002) Diabetes, 51, pp. 1907-1912. , PMID:12031980Holness, M.J., Smith, N.D., Greenwood, G.K., Sugden, M.C., Interactive influences of peroxisome proliferator-activated receptor alpha activation and glucocorticoids on pancreatic beta cell compensation in insulin resistance induced by dietary saturated fat in the rat (2005) Diabetologia, 48, pp. 2062-2068. , PMID:16132960Kahn, S.E., Hull, R.L., Utzschneider, K.M., Mechanisms linking obesity to insulin resistance and type 2 diabetes (2006) Nature, 444, pp. 840-846. , PMID:17167471Karlsson, S., Ostlund, B., Myrsén-Axcrona, U., Sundler, F., Ahrén, B., Beta cell adaptation to dexamethasone-induced insulin resistance in rats involves increased glucose responsiveness but not glucose effectiveness (2001) Pancreas, 22, pp. 148-156. , PMID:11249069Lin, K.H., Liou, T.L., Hsiao, L.C., Hwu, C.M., Clinical and biochemical indicators of homeostasis model assessment-estimated insulin resistance in postmenopausal women (2011) J. Chin. Med. Assoc, 74, pp. 442-447. , PMID:22036135Maedler, K., Schumann, D.M., Schulthess, F., Oberholzer, J., Bosco, D., Berney, T., Aging correlates with decreased beta-cell proliferative capacity and enhanced sensitivity to apoptosis: A potential role for Fas and pancreatic duodenal homeobox-1 (2006) Diabetes, 55, pp. 2455-2462. , PMID:16936193(2011) Guide for the Care and Use of Laboratory Animals, , www.nap.edu/catalog.php?record_id=12910, 8th Ed. National Academy Press, Washington, D.CNicod, N., Giusti, V., Besse, C., Tappy, L., Metabolic adaptations to dexamethasone-induced insulin resistance in healthy volunteers (2003) Obes. Res, 11, pp. 625-631. , PMID:12740452Novelli, M., De Tata, V., Bombara, M., Lorenzini, A., Masini, M., Pollera, M., Insufficient adaptive capability of pancreatic endocrine function in dexamethasone-treated ageing rats (1999) J. Endocrinol, 162, pp. 425-432. , PMID:10467234Ogawa, A., Johnson, J.H., Ohneda, M., McAllister, C.T., Inman, L., Alam, T., Roles of insulin resistance and beta-cell dysfunction in dexamethasoneinduced diabetes (1992) J. Clin. Invest, 90, pp. 497-504. , PMID: 1644920Ohneda, M., Johnson, J.H., Inman, L.R., Unger, R.H., GLUT-2 function in glucose-unresponsive beta cells of dexamethasone-induced diabetes in rats (1993) J. Clin. Invest, 92, pp. 1950-1956. , PMID:8408647Pacini, G., Valerio, A., Beccaro, F., Nosadini, R., Cobelli, C., Crepaldi, G., Insulin sensitivity and beta-cell responsivity are not decreased in elderly subjects with normal OGTT (1988) J. Am. Geriatr. Soc, 36, pp. 317-323. , PMID:3280644Palmer, J.P., Ensinck, J.W., Acute-phase insulin secretion and glucose tolerance in young and aged normal men and diabetic patients (1975) J. Clin. Endocrinol. Metab, 41, pp. 498-503. , PMID:1159058Rafacho, A., Roma, L.P., Taboga, S.R., Boschero, A.C., Bosqueiro, J.R., Dexamethasone-induced insulin resistance is associated with increased connexin 36 mRNA and protein expression in pancreatic rat islets (2007) Can. J. Physiol. Pharmacol, 85, pp. 536-545. , PMID:17632589Rafacho, A., Giozzet, V.A., Boschero, A.C., Bosqueiro, J.R., Functional alterations in endocrine pancreas of rats with different degrees of dexamethasone-induced insulin resistance (2008) Pancreas, 36, pp. 284-293. , PMID:18362843Rafacho, A., Ribeiro, D.L., Boschero, A.C., Taboga, S.R., Bosqueiro, J.R., Increased pancreatic islet mass is accompanied by activation of the insulin receptor substrate-2/serine-threonine kinase pathway and augmented cyclin D2 protein levels in insulin-resistant rats (2008) Int. J. Exp. Pathol, 89, pp. 264-275. , PMID:18429991Rafacho, A., Quallio, S., Ribeiro, D.L., Taboga, S.R., Paula, F.M., Boschero, A.C., The adaptive compensations in endocrine pancreas from glucocorticoid-treated rats are reversible after the interruption of treatment (2010) Acta Physiol, 200, pp. 223-235. , PMID:20456283Rafacho, A., Abrantes, J.L., Ribeiro, P.F.M., Pinto, M.E., Boschero, A.C., Morphofunctional alterations in endocrine pancreas of short- and longterm dexamethasone-treated rats (2011) Horm. Metab. Res, 43, pp. 275-281. , PMID:21225543Rafacho, A., Boschero, A.C., Ortsäter, H., Functional and molecular aspects of glucocorticoids in the endocrine pancreas and glucose homeostasis (2012) State of the Art of Therapeutic Endocrinology, , Edited by Dr. Sameh Magdeldin. InTechReaven, E., Curry, D., Moore, J., Reaven, G., Effect of age and environmental factors on insulin release from the perfused pancreas of the rat (1983) J. Clin. Invest, 71, pp. 345-350. , PMID:6337185Schäcke, H., Döcke, W.D., Asadullah, K., Mechanisms involved in the side effects of glucocorticoids (2002) Pharmacol. Ther, 96, pp. 23-43. , PMID:12441176Sengupta, P., A scientific review of age determination for a laboratory rat: How old is it in comparison with human age? (2011) Biomed. Int, 2, pp. 81-89Shimizu, M., Kawazu, S., Tomono, S., Ohno, T., Kato, N., Ishi, C., Age-related alteration of pancreatic beta-cell function. Increased proinsulin and proinsulin-to-insulin molar ratio in elderly, but not in obese, subjects without glucose intolerance (1996) Diabetes Care, 19, pp. 8-11. , PMID:8720525Song, Y., Manson, J.E., Tinker, L., Howard, B.V., Kuller, L.H., Nathan, L., Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in multiethnic cohort of women: The Women's Health Initiative Observational Study (2007) Diabetes Care, 30, pp. 1747-1752. , PMID:17468352Soriano, S., Ropero, A.B., Alonso-Magdalena, P., Ripoll, C., Quesada, I., Gassner, B., Rapid regulation of K(ATP) channel activity by 17{beta}-estradiol in pancreatic {beta}-cells involves the estrogen receptor {beta} and the atrial natriuretic peptide receptor (2009) Mol. Endocrinol, 23, pp. 1973-1982. , PMID:19855088Stojanovska, L., Rosella, G., Proietto, L., Evolution of dexamethasoneinduced insulin resistance in rats (1990) Am. J. Physiol, 258, pp. E748-E756. , PMID: 2185660Thunhorst, R.L., Beltz, T.G., Johnson, A.K., Glucocorticoids increase salt appetite by promoting water and sodium excretion (2007) Am. J. Physiol. Regul. Integr. Comp. Physiol, 293, pp. R1444-R1451. , PMID:17596327Tomas, F.M., The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone (1998) J. Endocrinol, 157, pp. 89-97. , PMID:9614362Vital, P., Larrieta, E., Hiriart, M., Sexual dimorphism in insulin sensitivity and susceptibility to develop diabetes in rats (2006) J. Endocrinol, 190, pp. 425-432. , PMID:16899575Weir, G.C., Bonner-Weir, S., Five stages of evolving beta-cell dysfunction during progression to diabetes (2004) Diabetes, 53, pp. S16-S21. , PMID:15561905Willi, S.M., Kennedy, A., Wallace, P., Ganaway, E., Rogers, N.L., Garvey, W.T., Troglitazone antagonizes metabolic effects of glucocorticoids in humans: Effects on glucose tolerance, insulin sensitivity, suppression of free fatty acids, and leptin (2002) Diabetes, 51, pp. 2895-2902. , PMID:12351424Xue, B., Kim, Y.B., Lee, A., Toschi, E., Bonner-Weir, S., Kahn, C.R., Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance (2007) J. Biol. Chem, 282, pp. 23829-23840. , PMID:1754516
Islet Neogenesis-associated Protein (ingap): The Role Of Its Endogenous Production As A Positive Modulator Of Insulin Secretion
No full textIslet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a "physiological" positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.1923034Pittenger, G.L., Vinik, A.I., Rosenberg, L., The partial isolation and characterization of ilotropin, a novel islet-specific growth factor (1992) Adv Exp Med Biol, 321, pp. 123-130Rafaeloff, R., Pittenger, G.L., Barlow, S.W., Qin, X.F., Yan, B., Rosenberg, L., Duguid, W.P., Vinik, A.I., Cloning and sequencing of the pancreatic islet neogenesis associated protein (INGAP) gene and its expression in islet neogenesis in hamsters (1997) J Clin Invest, 99, pp. 2100-2109Flores, L.E., García, M.E., Borelli, M.I., Del Zotto, H., Alzugaray, M.E., Maiztegui, B., Gagliardino, J.J., Expression of islet neogenesis-associated protein (INGAP) in islets of normal hamsters (2003) J Endocrinol, 177, pp. 243-248Del Zotto, H., Borelli, M.I., Flores, L., García, M.E., Gómez Dumm, C.L., Chicco, A., Lombardo, Y.B., Gagliardino, J.J., Islet neogenesis: an apparent key component of long-term pancreas adaptation to increased insulin demand (2004) J Endocrinol, 183, pp. 321-330Gagliardino, J.J., Del Zotto, H., Massa, L., Flores, L.E., Borelli, M.I., Pancreatic duodenal homeobox-1 and islet neogenesis-associated protein: a possible combined marker of activateable pancreatic cell precursors (2003) J Endocrinol, 177, pp. 249-259Barbosa, H., Bordin, S., Stoppiglia, L., Silva, K., Borelli, M., Del Zotto, H., Gagliardino, J., Boschero, A., Islet Neogenesis Associated Protein (INGAP) modulates gene expression in cultured neonatal rat islets (2006) Regul Pept, 136, pp. 78-84Barbosa, H.C., Bordin, S., Anhê, G., Persaud, S.J., Bowe, J., Borelli, M.I., Gagliardino, J.J., Boschero, A.C., Islet neogenesis-associated protein signaling in neonatal pancreatic rat islets: involvement of the cholinergic pathway (2008) J Endocrinol, 199, pp. 299-306Silva, K.E., Barbosa, H.C., Rafacho, A., Bosqueiro, J.R., Stoppiglia, L.F., Carneiro, E.M., Borelli, M.I., Boschero, A.C., INGAP-PP up-regulates the expression of genes and proteins related to K+ ATP channels and ameliorates Ca2+ handling in cultured adult rat islets (2008) Regul Pept, 148, pp. 39-45Madrid, V., Del Zotto, H., Maiztegui, B., Raschia, M.A., Alzugaray, M.E., Boschero, A.C., Barbosa, H.C., Gagliardino, J.J., Islet neogenesis-associated protein pentadecapeptide (INGAP-PP): mechanisms involved in its effect upon beta-cell mass and function (2009) Regul Pept, 157, pp. 25-31Paula, F.M., Barbosa, H.C., Carneiro, E.M., Persaud, S.J., Gagliardino, J.J., Boschero, A.C., Souza, K.L., Requirement of NF-kappaB signalling pathway for modulation of the cholinergic muscarinic M3 receptor expression by INGAP-PP in insulin-producing cells (2010) Eur J Pharmacol, 642, pp. 37-46Borelli, M.I., Stoppiglia, L.F., Rezende, L.F., Flores, L.E., Del Zotto, H., Boschero, A.C., Gagliardino, J.J., INGAP-related pentadecapeptide: its modulatory effect upon insulin secretion (2005) Regul Pept, 131, pp. 97-102Chang, T.J., Weaver, J.R., Bowman, A., Leone, K., Raab, R., Vinik, A.I., Pittenger, G.L., Taylor-Fishwick, D.A., Targeted expression of islet neogenesis associated protein to beta cells enhances glucose tolerance and confers resistance to streptozotocin-induced hyperglycemia (2011) Mol Cell Endocrinol, 335, pp. 104-109Taylor-Fishwick, D.A., Bowman, A., Hamblet, N., Bernard, P., Harlan, D.M., Vinik, A.I., Islet neogenesis associated protein transgenic mice are resistant to hyperglycemia induced by streptozotocin (2006) J Endocrinol, 190, pp. 729-737Kapur, R., Højfeldt, T.W., Mogensen, J.P., Shaw, A.C., Rønn, S.G., Karlsen, A.E., Heller, R.S., Short-term effects of INGAP and Reg family peptides on the appearance of small β-cells clusters in non-diabetic mice (2012) Islets, 4 (1)Zha, M., Zhang, M., Shan, S., Xu, K.F., Chen, H., Xu, X.Y., Qian, L., Yang, T., Effects of islet neogenesis-associated protein pentadecapeptide on cell mass and insulin secretion of pancreatic β-cells (2012) J Endocrinol Invest, 35, pp. 634-639Rosenberg, L., Lipsett, M., Yoon, J.W., Prentki, M., Wang, R., Jun, H.S., Pittenger, G.L., Vinik, A.I., A pentadecapeptide fragment of islet neogenesis-associated protein increases beta-cell mass and reverses diabetes in C57BL/6J mice (2004) Ann Surg, 240, pp. 875-884Dungan, K.M., Buse, J.B., Ratner, R.E., Effects of therapy in type 1 and type 2 diabetes mellitus with a peptide derived from islet neogenesis associated protein (INGAP) (2009) Diabetes Metab Res Rev, 25, pp. 558-565Pittenger, G.L., Taylor-Fishwick, D., Vinik, A.I., A role for islet neogenesis in curing diabetes (2009) Diabetologia, 52, pp. 735-738Lacy, P.E., Kostianovsky, M., Method for the isolation of intact islets of Langerhans from the rat pancreas (1967) Diabetes, 16, pp. 35-39Sambrook, J., Fritsch, E.F., Maniatis, T.E., (1989) Molecular cloning: a laboratory manual, , Cold Spring Harbor Laboratory Press, Cold Spring HarborTaylor-Fishwick, D.A., Rittman, S., Kendall, H., Roy, L., Shi, W., Cao, Y., Pittenger, G.L., Vinik, A.I., Cloning genomic INGAP: a Reg-related family member with distinct transcriptional regulation sites (2003) Biochim Biophys Acta, 1638, pp. 83-89Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Herbert, V., Lau, K.S., Gottlieb, C.W., Bleicher, S.J., Coated charcoal immunoassay of insulin (1965) J Clin Endocrinol Metab, 25, pp. 1375-1384Labarca, C., Paigen, K., A simple, rapid, and sensitive DNA assay procedure (1980) Anal Biochem, 102, pp. 344-352Del Zotto, H., Massa, L., Rafaeloff, R., Pittenger, G.L., Vinik, A., Gold, G., Reifel-Miller, A., Gagliardino, J.J., Possible relationship between changes in islet neogenesis and islet neogenesis-associated protein-positive cell mass induced by sucrose administration to normal hamsters (2000) J Endocrinol, 165, pp. 725-733Taylor-Fishwick, D.A., Bowman, A., Korngiebel-Rosique, M., Vinik, A.I., Pancreatic islet immunoreactivity to the Reg protein INGAP (2008) J Histochem Cytochem, 56, pp. 183-191Sha, J.P., Xue, Y.M., Chen, X., Long, K., Liang, H.C., Sang, D., Mao, R.R., Lin, Z., Small interfering RNA-mediated islet neogenesis associated protein gene silencing inhibits the proliferation of INS-1 islet cells (2009) Nan Fang Yi Ke Da Xue Xue Bao, 29, pp. 2040-2043Borelli, M.I., Del Zotto, H., Flores, L.E., García, M.E., Boschero, A.C., Gagliardino, J.J., Transcription, expression and tissue binding in vivo of INGAP and INGAP-related peptide in normal hamsters (2007) Regul Pept, 140, pp. 192-197Rosenberg, L., Kahlenberg, M., Vinik, A.I., Duguid, W.P., Paracrine/autocrine regulation of pancreatic islet cell proliferation and differentiation in the hamster: studies using parabiosis (1996) Clin Invest Med, 19, pp. 3-12Pipeleers, D.G., Schuit, F.C., in't Veld, P.A., Maes, E., Hooghe-Peters, E.L., Van de Winkel, M., Gepts, W., Interplay of nutrients and hormones in the regulation of insulin release (1985) Endocrinology, 117, pp. 824-833Li, J., Wang, Y., Yu, X., Chen, H., Wu, Y., Han, X., Guo, X., Yang, T., Islet neogensis-associated pretein-related pentadecapeptide enhances the differentiation of islet-like clusters from human pancreatic duct cells (2009) Peptides, 30, pp. 2242-224
Taurine Supplementation Increases Katp Channel Protein Content, Improving Ca2+ Handling And Insulin Secretion In Islets From Malnourished Mice Fed On A High-fat Diet
No full textPancreatic β-cells are highly sensitive to suboptimal or excess nutrients, as occurs in protein-malnutrition and obesity. Taurine (Tau) improves insulin secretion in response to nutrients and depolarizing agents. Here, we assessed the expression and function of Cav and KATP channels in islets from malnourished mice fed on a high-fat diet (HFD) and supplemented with Tau. Weaned mice received a normal (C) or a low-protein diet (R) for 6 weeks. Half of each group were fed a HFD for 8 weeks without (CH, RH) or with 5 % Tau since weaning (CHT, RHT). Isolated islets from R mice showed lower insulin release with glucose and depolarizing stimuli. In CH islets, insulin secretion was increased and this was associated with enhanced KATP inhibition and Cav activity. RH islets secreted less insulin at high K+ concentration and showed enhanced KATP activity. Tau supplementation normalized K+-induced secretion and enhanced glucose-induced Ca 2+ influx in RHT islets. R islets presented lower Ca2+ influx in response to tolbutamide, and higher protein content and activity of the Kir6.2 subunit of the KATP. Tau increased the protein content of the α1.2 subunit of the Cav channels and the SNARE proteins SNAP-25 and Synt-1 in CHT islets, whereas in RHT, Kir6.2 and Synt-1 proteins were increased. In conclusion, impaired islet function in R islets is related to higher content and activity of the KATP channels. Tau treatment enhanced RHT islet secretory capacity by improving the protein expression and inhibition of the KATP channels and enhancing Synt-1 islet content. © 2014 Springer-Verlag.46921232136Amaral, A.G., Rafacho, A., Machado De Oliveira, C.A., Batista, T.M., Ribeiro, R.A., Latorraca, M.Q., Boschero, A.C., Carneiro, E.M., Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice (2010) Pancreas, 39 (6), pp. 847-855Andersson, S.A., Olsson, A.H., Esguerra, J.L., Heimann, E., Ladenvall, C., Edlund, A., Salehi, A., Eliasson, L., Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes (2012) Mol Cell Endocrinol, 364 (1-2), pp. 36-45Araujo, E.P., De Souza, C.T., Ueno, M., Cintra, D.E., Bertolo, M.B., Carvalheira, J.B., Saad, M.J., Velloso, L.A., Infliximab restores glucose homeostasis in an animal model of diet-induced obesity and diabetes (2007) Endocrinology, 148 (12), pp. 5991-5997. , http://endo.endojournals.org/cgi/reprint/148/12/5991, DOI 10.1210/en.2007-0132Barker, D.J.P., Hales, C.N., Fall, C.H.D., Osmond, C., Phipps, K., Clark, P.M.S., Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): Relation to reduced fetal growth (1993) Diabetologia, 36 (1), pp. 62-67. , DOI 10.1007/BF00399095Batista, T.M., Ribeiro, R.A., Amaral, A.G., De Oliveira, C.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation restores glucose and carbachol-induced insulin secretion in islets from low-protein diet rats: Involvement of Ach-M3R, Synt 1 and SNAP-25 proteins (2012) J Nutr Biochem, 23 (3), pp. 306-312Batista, T.M., Da Silva, P.M., Amaral, A.G., Ribeiro, R.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation restores insulin secretion and reduces ER stress markers in protein-malnourished mice (2013) Adv Exp Med Biol, 776, pp. 129-139Batista, T.M., Ribeiro, R.A., Da Silva, P.M., Camargo, R.L., Lollo, P.C., Boschero, A.C., Carneiro, E.M., Taurine supplementation improves liver glucose control in normal protein and malnourished mice fed a high-fat diet (2013) Mol Nutr Food Res, 57 (3), pp. 423-434. , doi:10.1002/mnfr.201200345Bernardis, L.L., Patterson, B.D., Correlation between 'Lee index' and carcass fat content in weanling and adult female rats with hypothalamic lesions (1968) J Endocrinol, 40 (4), pp. 527-528Best, L., Jarman, E., Brown, P.D., A dual action of saturated fatty acids on electrical activity in rat pancreatic beta-cells. Role of volume-regulated anion channel and KATP channel currents (2011) J Physiol, 589 (PART 6), pp. 1307-1316Bol, V.V., Delattre, A.I., Reusens, B., Raes, M., Remacle, C., Forced catch-up growth after fetal protein restriction alters the adipose tissue gene expression program leading to obesity in adult mice (2009) Am J Physiol Regul Integr Comp Physiol, 297 (2), pp. R291-R299. , doi:10.1152/ajpregu.90497.2008Boschero, A.C., Malaisse, W.J., Stimulus-secretion coupling of glucose-induced insulin release. XXIX. Regulation of 86Rb+ efflux from perifused islets (1979) American Journal of Physiology Endocrinology Metabolism and Gastrointestinal Physiology, 5 (2), pp. E139-E146Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Branstrom, R., Aspinwall, C.A., Valimaki, S., Ostensson, C.-G., Tibell, A., Eckhard, M., Brandhorst, H., Larsson, O., Long-Chain CoA esters activate human pancreatic beta-cell KATP channels: Potential role in Type 2 diabetes (2004) Diabetologia, 47 (2), pp. 277-283. , DOI 10.1007/s00125-003-1299-xBustamante, J., Lobo, M.V., Alonso, F.J., Mukala, N.T., Gine, E., Solis, J.M., Tamarit-Rodriguez, J., Martin Del Rio, R., An osmotic-sensitive taurine pool is localized in rat pancreatic islet cells containing glucagon and somatostatin (2001) Am J Physiol Endocrinol Metab, 281 (6), pp. E1275-E1285Camargo, R.L., Batista, T.M., Ribeiro, R.A., Velloso, L.A., Boschero, A.C., Carneiro, E.M., Effects of taurine supplementation upon food intake and central insulin signaling in malnourished mice fed on a high-fat diet (2013) Adv Exp Med Biol, 776, pp. 93-103. , doi:10.1007/978-1-4614-6093-0-10Carneiro, E.M., Latorraca, M.Q., Araujo, E., Beltra, M., Oliveras, M.J., Navarro, M., Berna, G., Martin, F., Taurine supplementation modulates glucose homeostasis and islet function (2009) J Nutr Biochem, 20 (7), pp. 503-511Cnop, M., Welsh, N., Jonas, J.-C., Jorns, A., Lenzen, S., Eizirik, D.L., Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: Many differences, few similarities (2005) Diabetes, 54 (SUPPL. 2), pp. S97-S107. , http://diabetes.diabetesjournals.org/cgi/reprint/54/suppl_2/S97, DOI 10.2337/diabetes.54.suppl-2.S97Da Silva, P.M., Batista, T.M., Ribeiro, R.A., Zoppi, C.C., Boschero, A.C., Carneiro, E.M., Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: Effect of leucine supplementation (2012) Metabolism, 61 (5), pp. 721-732Delghingaro-Augusto, V., Ferreira, F., Bordin, S., Do Amaral, M.E., Toyama, M.H., Boschero, A.C., Carneiro, E.M., A low protein diet alters gene expression in rat pancreatic islets (2004) J Nutr, 134 (2), pp. 321-327Ferreira, F., Filiputti, E., Arantes, V.C., Stoppiglia, L.F., Araujo, E.P., Delghingaro-Augusto, V., Latorraca, M.Q., Carneiro, E.M., Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase Calpha expression (2003) Journal of Nutrition, 133 (3), pp. 695-699Ferreira, F., Barbosa, H.C.L., Stoppiglia, L.F., Delghingaro-Augusto, V., Pereira, E.A., Boschero, A.C., Carneiro, E.M., Decreased Insulin Secretion in Islets from Rats Fed a Low Protein Diet Is Associated with a Reduced PKAalpha Expression (2004) Journal of Nutrition, 134 (1), pp. 63-67Gribble, F.M., Reimann, F., Pharmacological modulation of K(ATP) channels (2002) Biochem Soc Trans, 30 (2), pp. 333-339Hales, C.N., Barker, D.J., Type 2 (non-insulin-dependent) diabetes mellitus: The thrifty phenotype hypothesis (1992) Diabetologia, 35 (7), pp. 595-601Han, J., Bae, J.H., Kim, S.-Y., Lee, H.-Y., Jang, B.-C., Lee, I.-K., Cho, C.-H., Song, D.-K., Taurine increases glucose sensitivity of UCP2-overexpressing beta-cells by ameliorating mitochondrial metabolism (2004) American Journal of Physiology - Endocrinology and Metabolism, 287 (5), pp. E1008-E1018. , DOI 10.1152/ajpendo.00008.2004Hoppa, M.B., Collins, S., Ramracheya, R., Hodson, L., Amisten, S., Zhang, Q., Johnson, P., Rorsman, P., Chronic palmitate exposure inhibits insulin secretion by dissociation of Ca(2 +) channels from secretory granules (2009) Cell Metab, 10 (6), pp. 455-465Iwashima, Y., Abiko, A., Ushikubi, F., Hata, A., Kaku, K., Sano, H., Eto, M., Downregulation of the voltage-dependent calcium channel (VDCC) beta-subunit mRNAs in pancreatic islets of type 2 diabetic rats (2001) Biochemical and Biophysical Research Communications, 280 (3), pp. 923-932. , DOI 10.1006/bbrc.2000.4122Lee, S.H., Lee, H.Y., Kim, S.Y., Lee, I.K., Song, D.K., Enhancing effect of taurine on glucose response in UCP2-overexpressing beta cells (2004) Diabetes Res Clin Pract, 66 (SUPPL. 1), pp. S69-S74Lim, J.-G., Lee, H.-Y., Yun, J.-E., Kim, S.-P., Park, J.-W., Suh, S.-I., Jang, B.-C., Song, D.-K., Taurine block of cloned ATP-sensitive K+ channels with different sulfonylurea receptor subunits expressed in Xenopus laevis oocytes (2004) Biochemical Pharmacology, 68 (5), pp. 901-910. , DOI 10.1016/j.bcp.2004.05.050, PII S0006295204003879Moritz, W., Leech, C.A., Ferrer, J., Habener, J.F., Regulated expression of adenosine triphosphate-sensitive potassium channel subunits in pancreatic beta-cells (2001) Endocrinology, 142 (1), pp. 129-138. , DOI 10.1210/en.142.1.129Nagamatsu, S., Nakamichi, Y., Yamamura, C., Matsushima, S., Watanabe, T., Ozawa, S., Furukawa, H., Ishida, H., Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: Restoration of decreased t-SNARE proteins improves impaired insulin secretion (1999) Diabetes, 48 (12), pp. 2367-2373Navarro, M., (2009) La Suplementación Con Taurina Modula la Homeostasis de la Glucosa Y la Función de Los Islotes Pancreáticos, , Universidad Pablo de Olavide Thesis Sevilla, España 2009Olofsson, C.S., Salehi, A., Holm, C., Rorsman, P., Palmitate increases L-type Ca2+ currents and the size of the readily releasable granule pool in mouse pancreatic beta-cells (2004) Journal of Physiology, 557 (3), pp. 935-948. , DOI 10.1113/jphysiol.2004.066258Park, E.-J., Bae, J.H., Kim, S.-Y., Lim, J.-G., Baek, W.-K., Kwon, T.K., Suh, S.-I., Song, D.-K., Inhibition of ATP-sensitive K+ channels by taurine through a benzamido-binding site on sulfonylurea receptor 1 (2004) Biochemical Pharmacology, 67 (6), pp. 1089-1096. , DOI 10.1016/j.bcp.2003.11.003, PII S0006295203008852Peng, Z., Xiaolei, Z., Al-Sanaban, H., Chengrui, X., Shengyi, Y., Ghrelin inhibits insulin release by regulating the expression of inwardly rectifying potassium channel 6.2 in islets (2012) Am J Med Sci, 343 (3), pp. 215-219Reis, M.A.B., Carneiro, E.M., Mello, M.A.R., Boschero, A.C., Saad, M.J.A., Velloso, L.A., Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats (1997) Journal of Nutrition, 127 (3), pp. 403-410Remacle, C., Dumortier, O., Bol, V., Goosse, K., Romanus, P., Theys, N., Bouckenooghe, T., Reusens, B., Intrauterine programming of the endocrine pancreas (2007) Diabetes Obes Metab, 9 (SUPPL. 2), pp. 196-209. , doi:10.1111/j.1463-1326.2007.00790.xRibeiro, R.A., Bonfleur, M.L., Amaral, A.G., Vanzela, E.C., Rocco, S.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets (2009) Diabetes Metab Res Rev, 25 (4), pp. 370-379Ribeiro, R.A., Vanzela, E.C., Oliveira, C.A., Bonfleur, M.L., Boschero, A.C., Carneiro, E.M., Taurine supplementation: Involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2 + handling in mouse pancreatic islets (2010) Br J Nutr, 104 (8), pp. 1148-1155Ribeiro, R.A., Santos-Silva, J.C., Vettorazzi, J.F., Cotrim, B.B., Mobiolli, D.D., Boschero, A.C., Carneiro, E.M., Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic beta-cells (2012) Amino Acids, 43 (4), pp. 1791-1801Rorsman, P., Braun, M., Zhang, Q., Regulation of calcium in pancreatic alpha- and beta-cells in health and disease (2012) Cell Calcium, 51 (3-4), pp. 300-308Sandovici, I., Smith, N.H., Nitert, M.D., Ackers-Johnson, M., Uribe-Lewis, S., Ito, Y., Jones, R.H., Ozanne, S.E., Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets (2011) Proc Natl Acad Sci USA, 108 (13), pp. 5449-5454. , doi:10.1073/pnas.1019007108Satoh, H., Sperelakis, N., Review of some actions of taurine on ion channels of cardiac muscle cells and others (1998) General Pharmacology, 30 (4), pp. 451-463. , DOI 10.1016/S0306-3623(97)00309-1, PII S0306362398003091Smith, A.J., Partridge, C.J., Asipu, A., Mair, L.A., Hunter, M., Sivaprasadarao, A., Increased ATP-sensitive K+ channel expression during acute glucose deprivation (2006) Biochemical and Biophysical Research Communications, 348 (3), pp. 1123-1131. , DOI 10.1016/j.bbrc.2006.07.170, PII S0006291X06017487Solon, C.S., Franci, D., Ignacio-Souza, L.M., Romanatto, T., Roman, E.A., Arruda, A.P., Morari, J., Velloso, L.A., Taurine enhances the anorexigenic effects of insulin in the hypothalamus of rats (2012) Amino Acids, 42 (6), pp. 2403-2410. , doi:10.1007/s00726-011-1045-5Soriano, S., Gonzalez, A., Marroqui, L., Tuduri, E., Vieira, E., Amaral, A.G., Batista, T.M., Quesada, I., Reduced insulin secretion in protein malnourished mice is associated with multiple changes in the beta-cell stimulus-secretion coupling (2010) Endocrinology, 151 (8), pp. 3543-3554Tokuyama, Y., Fan, Z., Furuta, H., Makielski, J.C., Polonsky, K.S., Bell, G.I., Yano, H., Rat inwardly rectifying potassium channel Kir6.2: Cloning, electrophysiological characterization, and decreased expression in pancreatic islets of male Zucker diabetic fatty rats (1996) Biochemical and Biophysical Research Communications, 220 (3), pp. 532-538. , DOI 10.1006/bbrc.1996.0439Tricarico, D., Barbieri, M., Camerino, D.C., Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor (2000) British Journal of Pharmacology, 130 (4), pp. 827-834Winzell, M.S., Magnusson, C., Ahren, B., Temporal and dietary fat content-dependent islet adaptation to high-fat feeding-induced glucose intolerance in mice (2007) Metabolism: Clinical and Experimental, 56 (1), pp. 122-128. , DOI 10.1016/j.metabol.2006.09.008, PII S0026049506003398Yang, S.N., Berggren, P.O., The role of voltage-gated calcium channels in pancreatic beta-cell physiology and pathophysiology (2006) Endocr Rev, 27 (6), pp. 621-67
Disruption Of Glucose Tolerance Caused By Glucocorticoid Excess In Rats Is Partially Prevented, But Not Attenuated, By Arjunolic Acid
No full textArjunolic acid (AA) obtained from plants of the Combretaceae family has shown anti-diabetic effects. Here, we analyzed whether the diabetogenic effects of dexamethasone (DEX) treatment on glucose homeostasis may be prevented or attenuated by the concomitant administration of AA. Adult Wistar rats were assigned to the following groups: vehicle-treated (Ctl), DEX-treated (1 mg/kg body weight intraperitoneally for 5 days) (Dex), AA-treated (30 mg/kg body weight by oral gavage twice per day) (Aa), AA treatment previous to and concomitant to DEX treatment (AaDex), and AA treatment after initiation of DEX treatment (DexAa). AA administration significantly ameliorated (AaDex) (P>0.05), but did not attenuate (DexAa), the glucose intolerance induced by DEX treatment. AA did not prevent or attenuate the elevation in hepatic glycogen and triacylglycerol content caused by DEX treatment. All DEX-treated rats exhibited hepatic steatosis that seemed to be more pronounced when associated with AA treatment given for a prolonged period (AaDex). Markers of liver function and oxidative stress were not significantly altered among the groups. Therefore, AA administered for a prolonged period partially prevents the glucose intolerance induced by DEX treatment, but it fails to produce this beneficial effect when given after initiation of GC treatment. Since AA may promote further hepatic steatosis when co-administered with GCs, care is required when considering this phytochemical as a hypoglycemiant and/or insulin-sensitizing agent.5210972982Ortsäter, H., Sjöholm, A., Rafacho, A., Regulation of glucocorticoid receptor signaling and the diabetogenic effects of glucocorticoid excess (2012) State of the art of therapeutic endocrinology, p. 1. , InTech, RijekaRhen, T., Cidlowski, J.A., Antiinflammatory action of glucocorticoids: New mechanisms for old drugs (2005) N Engl J Med, 353, p. 1711Schäcke, H., Döcke, W.D., Asadullah, K., Mechanims involved in the side effects of glucocorticoids (2002) Pharmacol Ther, 96, p. 23Wajngot, A., Giacca, A., Grill, V., Vranic, M., Efendic, S., The diabetogenic effects of glucocorticoids are more pronounced in low- than in high-insulin responders (1992) Proc Natl Acad Sci USA, 89, p. 6035Schneiter, P., Tappy, L., Kinetics of dexamethasone-induced alterations of glucose metabolism in healthy humans (1998) Am J Physiol, 275, p. E806Nicod, N., Giusti, V., Besse, C., Tappy, L., Metabolic adaptations to dexamethasone-induced insulin resistance in healthy volunteers (2003) Obes Res, 11, p. 625Rafacho, A., Quallio, S., Ribeiro, D.L., Taboga, S.R., Paula, F.M., Boschero, A.C., Bosqueiro, J.R., The adaptive compensations in endocrine pancreas from glucocorticoid-treated rats are reversible after the interruption of treatment (2010) Acta Physiol, 200, p. 223Rafacho, A., Abrantes, J.L., Ribeiro, D.L., Paula, F.M., Pinto, M.E., Boschero, A.C., Bosqueiro, J.R., Morphofunctional alterations in endocrine pancreas of short- and long-term dexamethasone-treated rats (2011) Horm Metab Res, 43, p. 275Rafacho, A., Boschero, A.C., Ortsäter, H., Functional and molecular aspects of glucocorticoid in the endocrine pancreas and glucose homeostasis (2012) State of the art of therapeutic endocrinology, p. 121. , InTech, RijekaVan Raalte, D.H., Nofrate, V., Bunck, M.C., Van Iersel, T., Elassaiss Schaap, J., Nässander, U.K., Heine, R.J., Diamant, M., Acute and 2-week exposure to prednisolone impair different aspects of beta-cell function in healthy men (2010) Eur J Endocrinol, 162, p. 729Willi, S.M., Kennedy, A., Wallace, P., Ganaway, E., Rogers, N.L., Garvey, W.T., Troglitazone antagonizes metabolic effects of glucocorticoids in humans: Effects on glucose tolerance, insulin sensitivity, suppression of free fatty acids, and leptin (2002) Diabetes, 51, p. 2895Thomas, C.R., Turner, S.L., Jefferson, W.H., Bailey, C.J., Prevention of dexamethasone-induced insulin resistance by metformin (1998) Biochem Pharmacol, 56, p. 1145Ragavan, B., Krishnakumari, S., Effect of terminalia arjuna stem bark extract on the activities of marker enzymes in alloxan induced diabetic rats (2005) AncSci Life, 25, p. 8Ragavan, B., Krishnakumari, S., Antidiabetic effect of T. arjuna bark extract in alloxan induced diabetic rats (2006) Indian J Clin Biochem, 21, p. 123Manna, P., Sinha, M., Sil, P.C., Protective role of arjunolic acid in response to streptozotocin-induced type-I diabetes via the mitochondrial dependent and independent pathways (2009) Toxicology, 257, p. 53Biswas, M., Kar, B., Bhattacharya, S., Kumar, R.B., Ghosh, A.K., Haldar, P.K., Antihyperglycemic activity and antioxidant role of Terminalia arjuna leaf in streptozotocin-induced diabetic rats (2011) Pharm Biol, 49, p. 335Manna, P., Das, J., Ghosh, J., Sil, P.C., Contribution of type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PARP, IkappaBalpha/NF- kappaB, MAPKs, and mitochondria-dependent pathways: Prophylatic role of arjunolic acid (2010) Free RadicBiol Med, 48, p. 1465Facundo, V., Rios, K.A., Medeiros, C.M., Militão, J.S.L.T., Miranda, A.L., Epifanio, R.A., Carvalho, M.P., Rezende, C.M., Arjunolic acid ethanolic extract of Combretum leprosum root and its use as a potential multi-functional phytomedicine and drug for neurodegenerative disorders: Anti-inflammatory and anticholinesterasic activities (2005) J Braz Chem Soc, 16, p. 1309Rafacho, A., Marroquí, L., Taboga, S.R., Abrantes, J.L., Silveira, L.R., Boschero, A.C., Carneiro, E.M., Quesada, I., Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus- secretion coupling in isolated rat islets (2010) Endocrinology, 151, p. 85Paula, F.M., Boschero, A.C., Carneiro, E.M., Bosqueiro, J.R., Rafacho, A., Insulin signaling proteins in pancreatic islets of insulin-resistant rats induced by glucocorticoid (2011) Biol Res, 44, p. 251Matthews, D.R., Hosker, J.P., Rudenski, A.S., Naylor, B.A., Treacher, D.F., Turner, R.C., Homeostatic model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man (1985) Diabetologia, 28, p. 412Guerrero-Romero, F., Simental-Mendia, L.E., Gonzalez-Ortiz, M., Martínez-Abundis, E., Ramos-Zavala, M.G., Hernández-Gonzales, S.O., Jacques-Camarena, O., Rodríguez-Morán, M., The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic- hyperinsulinemic clamp (2010) J Clin Endocrinol Metab, 95, p. 3347Lo, S., Russell, J.C., Taylor, A.W., Determination of glycogen in small tissue samples (1970) J Appl Physiol, 28, p. 234Giozzet, V.A., Rafacho, A., Boschero, A.C., Carneiro, E.M., Bosqueiro, J.R., Dexamethasone treatment in vivo counteracts the functional pancreatic islet alterations caused by malnourishment in rats (2008) Metabolism, 57, p. 617Tietze, F., Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues (1969) Anal Biochem, 27, p. 502Draper, H.H., Hadley, M., Malondialdehyde determination as index of lipid peroxidation (1990) Methods Enzymol, 186, p. 421Reznick, A.Z., Packer, L., Oxidative damage to proteins: Spectrophotometric method for carbonyl assay (1994) Methods Enzymol, 233, p. 357Weir, G.C., Bonner-Weir, S., Five stages evolving beta-cell dysfunction during progression to diabetes Diabetes, 53 (2004) suppl, 3, p. S16Burén, J., Lai, Y.C., Lungdren, M., Eriksson, J.W., Jensen, J., Insulin action and insulin signaling in fat and muscle from dexamethasone-treated rats (2008) Arch Biochem Biophys, 474, p. 91Mokuda, O., Sakamoto, Y., Ikeda, T., Mashiba, H., Sensitivity and responsiveness of glucose output to insulin in isolated perfused liver from dexamethasone-treated rats (1991) Horm Metab Res, 23, p. 53Longano, C.A., Fletcher, H.P., Insulin release after acute hydrocortisone treatment in mice (1983) Metabolism, 32, p. 603Manna, P., Sil, P.C., Impaired redox signaling and mitochondrial uncoupling contributes vascular inflammation and cardiac dysfunction in type 1 diabetes (2012) Protective role of arjunolic acid, Biochimie, 94, p. 786Muoio, D.M., Newgard, C.B., Obesity-related derangements in metabolic regulation (2006) Annu Rev Biochem, 75, p. 36
Reduced Pancreatic β-cell Mass Is Associated With Decreased Foxo1 And Erk1/2 Protein Phosphorylation In Low-protein Malnourished Rats
Get PDFA low-protein diet leads to functional and structural pancreatic islet alterations, including islet hypotrophy. Insulin-signaling pathways are involved in several adaptive responses by pancreatic islets. We determined the levels of some insulin-signaling proteins related to pancreatic islet function and growth in malnourished rats. Adult male Wistar rats (N = 20 per group) were fed a 17% protein (normal-protein diet; NP) or 6% protein (low-protein diet; LP), for 8 weeks. At the end of this period, blood glucose and serum insulin and albumin levels were measured. The morphometric parameters of the endocrine pancreas and the content of some proteins in islet lysates were determined. The β-cell mass was significantly reduced (≅65%) in normoglycemic but hypoinsulinemic LP rats compared to NP rats. Associated with these alterations, a significant 30% reduction in insulin receptor substrate-1 and a 70% increase in insulin receptor substrate-2 protein content were observed in LP islets compared to NP islets. The phosphorylated serine-threonine protein kinase (pAkt)/Akt protein ratio was similar in LP and NP islets. The phosphorylated forkhead-O1 (pFoxO1)/FoxO1 protein ratio was decreased by 43% in LP islets compared to NP islets (P < 0.05). Finally, the ratio of phosphorylated-extracellular signal-related kinase 1/2 (pErk1/2) to total Erk1/2 protein levels was decreased by 71% in LP islets compared to NP islets (P < 0.05). Therefore, the reduced β-cell mass observed in LP rats is associated with the reduction of phosphorylation in mitogenic-related signals, FoxO1 and Erk proteins. The cause/effect basis of this association remains to be determined.4210935941Snoeck, A., Remacle, C., Reusens, B., Hoet, J.J., Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas (1990) Biology of the Neonate, 57 (2), pp. 107-118Dahri, S., Snoeck, A., Reusens-Billen, B., Remacle, C., Hoet, J.J., Islet function in offspring of mothers on low-protein diet during gestation (1991) Diabetes, 40 (SUPPL. 2), pp. 115-120Petrik, J., Reusens, B., Arany, E., Remacle, C., Coelho, C., Hoet, J.J., Hill, D.J., A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II (1999) Endocrinology, 140 (10), pp. 4861-4873Dumortier, O., Blondeau, B., Duvillie, B., Reusens, B., Breant, B., Remacle, C., Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet (2007) Diabetologia, 50 (12), pp. 2495-2503. , DOI 10.1007/s00125-007-0811-0Ferreira, F., Filiputti, E., Arantes, V.C., Stoppiglia, L.F., Araujo, E.P., Delghingaro-Augusto, V., Latorraca, M.Q., Carneiro, E.M., Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase C alpha expression (2003) Journal of Nutrition, 133 (3), pp. 695-699Giozzet, V.A.G., Rafacho, A., Boschero, A.C., Carneiro, E.M., Bosqueiro, J.R., Dexamethasone treatment in vivo counteracts the functional pancreatic islet alterations caused by malnourishment in rats (2008) Metabolism: Clinical and Experimental, 57 (5), pp. 617-624. , DOI 10.1016/j.metabol.2007.12.004, PII S0026049508000139Reis, M.A., Carneiro, E.M., Mello, M.A., Boschero, A.C., Saad, M.J., Velloso, L.A., Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats (1997) J Nutr, 127, pp. 403-410Swenne, I., Borg, L.A., Crace, C.J., Schnell, L.A., Persistent reduction of pancreatic beta-cell mass after a limited period of protein-energy malnutrition in the young rat (1992) Diabetologia, 35, pp. 939-945Tse, E.O., Gregoire, F.M., Reusens, B., Remacle, C., Hoet, J.J., Johnson, P.R., Changes of islet size and islet size distribution resulting from protein-malnutrition in lean (Fa/Fa) and obese (fa/fa) Zucker rats (1997) Obes Res, 5, pp. 563-571Liu, Y.Q., Jetton, T.L., Leahy, J.L., Beta-cell adaptation to insulin resistance. Increased pyruvate carboxylase and malate-pyruvate shuttle activity in islets of nondiabetic Zucker fatty rats (2002) J Biol Chem, 277, pp. 39163-39168Prentki, M., Nolan, C.J., Islet beta cell failure in type 2 diabetes (2006) Journal of Clinical Investigation, 116 (7), pp. 1802-1812. , http://www.jci.org/cgi/reprint/116/7/1802.pdf, DOI 10.1172/JCI29103Rafacho, A., Giozzet, V.A., Boschero, A.C., Bosqueiro, J.R., Functional alterations in endocrine pancreas of rats with different degrees of dexamethasone-induced insulin resistance (2008) Pancreas, 36, pp. 284-293Jetton, T.L., Everill, B., Lausier, J., Roskens, V., Habibovic, A., LaRock, K., Enhanced beta-cell mass without increased proliferation following chronic mild glucose infusion (2008) Am J Physiol Endocrinol Metab, 294, pp. E679-E687Kasuga, M., Karlsson, F.A., Kahn, C.R., Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor (1982) Science, 215 (4529), pp. 185-187Ullrich, A., Bell, J.R., Chen, E.Y., Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes (1985) Nature, 313 (6005), pp. 756-761. , DOI 10.1038/313756a0Backer, J.M., Myers Jr., M.G., Shoelson, S.E., Chin, D.J., Sun, X.J., Miralpeix, M., Phosphatidylinositol 3′-kinase is activated by association with IRS-1 during insulin stimulation (1992) EMBO J, 11, pp. 3469-3479Saad, M.J., Molecular mechanisms of insulin resistance (1994) Braz J Med Biol Res, 27, pp. 941-957Sesti, G., Federici, M., Hribal, M.L., Lauro, D., Sbraccia, P., Lauro, R., Defects of the insulin receptor substrate (IRS) system in human metabolic disorders (2001) FASEB Journal, 15 (12), pp. 2099-2111. , DOI 10.1096/fj.01-0009revRafacho, A., Roma, L.P., Taboga, S.R., Boschero, A.C., Bosqueiro, J.R., Dexamethasone-induced insulin resistance is associated with increased connexin 36 mRNA and protein expression in pancreatic rat islets (2007) Canadian Journal of Physiology and Pharmacology, 85 (5), pp. 536-545. , DOI 10.1139/Y07-037Rafacho, A., Ribeiro, D.L., Boschero, A.C., Taboga, S.R., Bosqueiro, J.R., Increased pancreatic islet mass is accompanied by activation of the insulin receptor substrate-2/serine-threonine kinase pathway and augmented cyclin D2 protein levels in insulin-resistant rats (2008) International Journal of Experimental Pathology, 89 (4), pp. 264-275. , DOI 10.1111/j.1365-2613.2008.00588.xRafacho, A., Cestari, T.M., Taboga, S.R., Boschero, A.C., Bosqueiro, J.R., High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets (2009) Am J Physiol Endocrinol Metab, 296, pp. E681-E689Saltiel, A.R., Kahn, C.R., Insulin signalling and the regulation of glucose and lipid metabolism (2001) Nature, 414 (6865), pp. 799-806. , DOI 10.1038/414799aKulkarni, R.N., Receptors for insulin and insulin-like growth factor-1 and insulin receptor substrate-1 mediate pathways that regulate islet function (2002) Biochem Soc Trans, 30, pp. 317-322Okada, T., Chong, W.L., Hu, J., Hinault, C., Michael, M.D., Krutzfeldt, J., Yin, C., Kulkarni, R.N., Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance (2007) Proceedings of the National Academy of Sciences of the United States of America, 104 (21), pp. 8977-8982. , DOI 10.1073/pnas.0608703104Porzio, O., Federici, M., Hribal, M.L., Lauro, D., Accili, D., Lauro, R., The Gly972→Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic beta cells (1999) J Clin Invest, 104, pp. 357-364Kulkarni, R.N., Winnay, J.N., Daniels, M., Bruning, J.C., Flier, S.N., Hanahan, D., Kahn, C.R., Altered function of insulin receptor substrate 1-deficient mouse islets and cultured beta-cell lines (1999) Journal of Clinical Investigation, 104 (12), pp. R69-R75Hennige, A.M., Ozcan, U., Okada, T., Jhala, U.S., Schubert, M., White, M.F., Kulkarni, R.N., Alterations in growth and apoptosis of insulin receptor substrate-1-deficient beta-cells (2005) American Journal of Physiology - Endocrinology and Metabolism, 289 (2), pp. E337-E346. , DOI 10.1152/ajpendo.00032.2004Withers, D.J., Gutierrez, J.S., Towery, H., Burks, D.J., Ren, J.-M., Previs, S., Zhang, Y., White, M.F., Disruption of IRS-2 causes type 2 diabetes in mice (1998) Nature, 391 (6670), pp. 900-904. , DOI 10.1038/36116Niessen, M., On the role of IRS2 in the regulation of functional beta-cell mass (2006) Archives of Physiology and Biochemistry, 112 (2), pp. 65-73. , DOI 10.1080/13813450600711409, PII N0HRTV1317M65040Downward, J., Mechanisms and consequences of activation of protein kinase B/Akt (1998) Current Opinion in Cell Biology, 10 (2), pp. 262-267. , DOI 10.1016/S0955-0674(98)80149-XCho, H., Thorvaldsen, J.L., Chu, Q., Feng, F., Birnbaum, M.J., Akt1/PKBalpha Is Required for Normal Growth but Dispensable for Maintenance of Glucose Homeostasis in Mice (2001) Journal of Biological Chemistry, 276 (42), pp. 38349-38352. , DOI 10.1074/jbc.C100462200Kitamura, T., Ido Kitamura, Y., Role of FoxO proteins in pancreatic beta cells (2007) Endocrine Journal, 54 (4), pp. 507-515. , http://www.jstage.jst.go.jp/article/endocrj/54/4/507/_pdf, DOI 10.1507/endocrj.KR-109Johnson, J.D., Ahmed, N.T., Luciani, D.S., Han, Z., Tran, H., Fujita, J., Misler, S., Polonsky, K.S., Increased islet apoptosis in Pdx1+/- mice (2003) Journal of Clinical Investigation, 111 (8), pp. 1147-1160. , DOI 10.1172/JCI200316537Okamoto, H., Nakae, J., Kitamura, T., Park, B.-C., Dragatsis, I., Accili, D., Transgenic rescue of insulin receptor-deficient mice (2004) Journal of Clinical Investigation, 114 (2), pp. 214-223. , DOI 10.1172/JCI200421645Kitamura, T., Nakae, J., Kitamura, Y., Kido, Y., Biggs III, W.H., Wright, C.V.E., White, M.F., Accili, D., The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth (2002) Journal of Clinical Investigation, 110 (12), pp. 1839-1847. , DOI 10.1172/JCI200216857Mordret, G., MAP kinase kinase: A node connecting multiple pathways (1993) Biology of the Cell, 79 (3), pp. 193-207. , DOI 10.1016/0248-4900(93)90138-5Marshall, C.J., MAP kinase kinase kinase, MAP kinase kinase and MAP kinase (1994) Curr Opin Genet Dev, 4, pp. 82-89Giorgetti, S., Pelicci, P.G., Pelicci, G., Von Obberghen, E., Involvement of Src-homology/collagen (SHC) proteins in signaling through the insulin receptor and the insulin-like-growth-factor-I-receptor (1994) European Journal of Biochemistry, 223 (1), pp. 195-202. , DOI 10.1111/j.1432-1033.1994.tb18983.xHolt, K.H., Kasson, B.G., Pessin, J.E., Insulin stimulation of a MEK-dependent but ERK-independent SOS protein kinase (1996) Molecular and Cellular Biology, 16 (2), pp. 577-583Lingohr, M.K., Dickson, L.M., McCuaig, J.F., Hugl, S.R., Twardzik, D.R., Rhodes, C.J., Activation of IRS-2-mediated signal transduction by IGF-1, but not TGF-alpha or EGF, augments pancreatic beta-cell proliferation (2002) Diabetes, 51, pp. 966-97
Protein Deficiency Attenuates The Effects Of Alloxan On Insulin Secretion And Glucose Homeostasis In Rats
No full textWe have investigated the effect of alloxan on insulin secretion and glucose homeostasis in rats maintained on a 17% protein (normal protein, NP) or 6% protein (low protein, LP) diet from weaning (21 days old) to adulthood (90 days old). The incidence of alloxan diabetes was higher in the NP (3.5 times) than in the LP group. During an oral glucose tolerance test, the area under serum glucose curve was lower in LP (57%) than in NP rats while there were no differences between the two groups in the area under serum insulin curve. The serum glucose disappearance rate (Kitt) after exogenous insulin administration was higher in LP (50%) than in NP rats. In pancreatic islets isolated from rats not injected with alloxan, acute exposure to alloxan (0.05 mmol/L) reduced the glucose- or arginine-stimulated insulin secretion of NP islets by 78% and 56%, respectively, whereas for islets from LP rats, the reduction was 47% and 17% in the presence of glucose and arginine, respectively. Alloxan treatment reduced the glucose oxidation in islets from LP rats to a lesser extent than in NP islets (23% vs. 56%). In conclusion, alloxan was less effective in producing hyperglycemia in rats fed a low protein diet than in normal diet rats. This effect is attributable to an increased peripheral sensivity to insulin in addition to a better preservation of glucose oxidation and insulin secretion in islets from rats fed a low protein diet.3317382Blachier, F., Murtada, A., Sener, A., Malaisse, W.J., Stimulus-secretion coupling of arginine-induced insulin release. Uptake of metabolized and nonmetabolized cationic amino acids by pancreatic islets (1989) Endocrinology, 124, pp. 134-141Borg, A.H., Cagliero, E., Sandler, S., Eizirik, D.L., Welsh, N., Welsh, M., Interleukin-1 B increases the activity of superoxide dismutase in rat pancreatic islet (1992) Endocrinology, 130, pp. 2851-2857Brooks, S.E.H., Patch, F.R., Golden, M.H.N., Payne-Robinson, H.M., Ultrastructure of the islets of Langerhans in protein energy malnutrition (1993) W.I. Med. J., 42, pp. 101-106Carneiro, E.M., Mello, M.A.R., Gobatto, C.A., Boschero, A.C., Low protein diet impairs glucose induced insulin release and 45Ca uptake by pancreatic rat islets (1995) Nutr. Biochem., 6, pp. 314-318Grace, C.J., Swenne, I., Khon, P.G., Strain, A.J., Milner, R.D.G., Protein energy malnutrition induces changes in insulin sensitivity (1990) Diabetes Metabol., 16, pp. 484-491De Vos, A., Heimberg, H., Quartier, E., Huypens, P., Bouwens, L., Pipeleers, D., Schuit, F., Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression (1995) J. Clin. Invest., 96, pp. 2489-2495Desai, M., Crowter, N.J., Lucas, A., Hales, C.N., Organ selective growth in the offspring of protein restricted mothers (1996) Br. J. Nutr., 76, pp. 591-603Dixit, P.K., Kaung, K.L.C., Pancreatic B cell in malnutrition: A study involving morphometric analysis and alloxan effects (1985) J. Nutr., 115, pp. 375-381Eizirik, D.L., Bjorklund, A., Cagliero, E., Genotoxic agents increase the expression of growth arrest and DNA damage-induced genes gadd 153 and gadd 45 in rat pancreatic islets (1993) Diabetes, 42, pp. 438-445Eizirik, D.L., Welsh, M., Strandell, E., Welsh, N., Sandler, S., Interleukin-1 B depletes insulin messenger RNA and increases heat shock protein Hsp 70 in mouse pancreatic islets without impairing glucose metabolism (1990) Endocrinology, 127, pp. 2290-2297Escriva, F., Kergoat, M., Bailbé, D., Pascual-Leone, A.M., Portha, B., Increased insulin action in the rat after protein malnutrition early in life (1991) Diabetologia, 34, pp. 559-564Gasa, R., Senner, A., Malaisse, W.J., Gomis, R., Apparent starvation induced repression of pancreatic islet glucokiriase (1995) Biochem. Mol. Med., 56, pp. 99-103James, W.P.T., Coore, H.G., Persistent impairment of insulin secretion and glucose tolerance after malnutrition (1970) Am. J. Clin. Nutr., 23, pp. 386-389Latorraca, M.Q., Carneiro, E.M., Mello, M.A.R., Boschero, A.C., Protein deficiency during pregnancy and lactation impairs glucose induced insulin secretion but increases the sensitivity to insulin in weaned rats (1998) Br. J. Nutr., 80, pp. 291-297Lenzen, S., Panten, U., Alloxan: History and mechanism of action (1988) Diahetologia, 31, pp. 337-342Lundebaek, K., Intravenous glucose tolerance as a tool in definition and diagnosis of diabetes mellitus (1962) Br. Med. J., 3, pp. 1057-1513Malaisse, W.J., Alloxan toxicity to B cell: A new hypothesis (1982) Biochem. Pharmacol., 31, pp. 3527-3534Malaisse, W.J., Malaisse-Lagae, F., Wright, P., Effect of fasting upon insulin secretion in the rat (1967) Am. J. Physiol., 213, pp. 843-848Mathews, J.N.S., Altman, D.G., Campbel, M.S., Royston, P., Analysis of serial measurements in medical research (1990) Br. Med. J., 27, pp. 230-235Matschinsky, F., Glucokinase as a sensor and metabolic signal generator in pancreatic β-cell and hepatocytes (1990) Diabetes, 39, pp. 647-652Mello, M.A.R., Cury, L., Valle, L.B.S., Oliveira-Filho, R.M., Pregnancy in young rats: Effects of malnutrition (1987) Nutr. Rep. Int., 36, pp. 527-535Mello, M.A.R., Luciano, E., Effects of protein malnutrition on glucose tolerance in rats with alloxan induced diabetes (1995) Braz. J. Med. Biol. Res., 28, pp. 467-470Munday, R., Ludwig, K., Lenzen, S., The relationship between the physicochemical properties and the biological effects of alloxan and several N-alkyl substituted alloxan derivatives (1993) J. Endocrinol., 139, pp. 153-163Nogueira, D.M., Strufaldi, B., Hirata, M.H., Abdula, D.S.P., Hirata, R.D.C., (1990) Métodos de Bioquimica Clínica, , São Paulo, SP, PancastOkitolonda, W., Brichard, S.M., Henquin, J.C., Repercussion of chronic protein calorie malnutrition on glucose homeostasis in the rat (1987) Diabetologia, 30, pp. 946-951Reis, A.B., Carneiro, E.M., Mello, M.A.R., Boschero, A.C., Saad, W.A., Velloso, L.A., Glucose induced insulin secretion is impaired and insulin induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein deficient rats (1997) J. Nutr., 127, pp. 403-410Sanches-Magalet, V., Goldfine, I.D., Vlahos, C.J., Sung, C.K., Role of phosphatidylinositol 3-kinase in insulin receptor signaling: Studies with the inhibitor LY 294002 (1994) Biochem. Biophys. Res. Commun., 204, pp. 446-452Scheynius, A., Taljedal, I.B., On the mechanism of glucose protection against alloxan toxicity (1971) Diabetologia, 7, pp. 252-255Scott, A.M., Atwater, I., Rojas, E., A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans (1981) Diabetologia, 21, pp. 470-475Smith, P.A., Sakura, H., Coles, B., Gummerson, N., Proks, P., Aschcroft, P.M., Electrogenic arginine transport mediates stimulus-secretion coupling in mouse pancreatic B cells (1997) J. Physiol., 499, pp. 625-635Stephens, J.M., Pilch, P.F., The metabolic regulation and vesicular transport of GLUT4, the major insulin-responsive glucose transporter (1995) Endocrine Rev., 16, pp. 529-546Swenne, I., Crace, C.J., Milner, R.D.G., Persistent impairment of insulin secretory response to glucose in adult rats after a limited period of protein-calorie malnutrition early in life (1987) Diabetes, 36, pp. 454-458Torun, B., Chew, F., Protein-energy malnutrition (1994) Modern Nutrition in Health and Disease, 2, pp. 950-976. , Shils, M., Olson, J.A. and Shike, M. (eds) Lea & Febiger, PhiladelphiaYoung, R., Dixit, P.K., Lack of diabetogenic effect of alloxan in protein-calorie malnourished rats (1980) J. Nutr., 110, pp. 703-70
Effects Of Taurine Supplementation Upon Food Intake And Central Insulin Signaling In Malnourished Mice Fed On A High-fat Diet
No full textFeeding behavior is a major determinant of body composition, adiposity, and glucose homeostasis. Both obesity and malnutrition are risk factors for the metabolic syndrome and are associated with altered food intake. Here we assessed the effects of taurine (TAU) supplementation upon adiposity, food intake, and central insulin signaling in malnourished mice fed on a high-fat diet (HFD). Weaned male C57BL/6 mice were fed a control (14% protein-C) or a protein-restricted (6% protein- R) diet. After 6 weeks, both groups received or not HFD for 8 weeks (CH and RH). Half of the HFD groups were supplemented with 5% TAU (CHT and RHT). Both HFD groups were overweight and showed increased perigonadal and retroperitoneal fat pads. TAU supplementation attenuated obesity in CHT but not in RHT mice. HFD induced hypercholesterolemia and glucose intolerance, although only CH group presented fasting hyperglycemia. TAU supplementation also improved glucose homeostasis only in CHT mice. Western blot analysis showed a reduction of 55% in CH hypothalamic content of phosphorylated IRS-1 (pIRS-1) at basal condition compared with C. TAU treatment increased 35% Akt phosphorylation levels in CHT without modification in RHT hypothalamus. However, TAU supplementation did not alter hypothalamic pIRS-1 amount. CH and RH mice presented increased calorie intake that was normalized in CHT but not in RHT. In conclusion, mice fed on an HFD developed obesity, hypercholesterolemia, glucose intolerance, and increased calorie intake. TAU promoted increased hypothalamic insulin action only in CH mice which was linked to prevention of overfeeding, obesity, and glucose intolerance. Protein-restriction promoted metabolic damages that were not prevented by TAU supplementation. © Springer Science+Business Media New York 2013.77693103Amaral, M.E., Barbuio, R., Milanski, M., Romanatto, T., Barbosa, H.C., Nadruz, W., Bertolo, M.B., Velloso, L.A., Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters (2006) J Neurochem, 98, pp. 203-212Badman, M.K., Flier, J.S., The gut and energy balance: Visceral allies in the obesity wars (2005) Science, 307, pp. 1909-1914Barker, D.J., Martyn, C.N., Osmond, C., Hales, C.N., Fall, C.H., Growth in utero and serum cholesterol concentrations in adult life (1993) BMJ, 307, pp. 1524-1527Batista, T.M., Ribeiro, R.A., Amaral, A.G., De Oliveira, C.A., Boschero, A.C., Carneiro, E.M., Taurine supplementation restores glucose and carbachol-induced insulin secretion in islets from lowprotein diet rats: Involvement of Ach-M3R, Synt 1 and SNAP-25 proteins (2012) J Nutr Biochem, 23, pp. 306-312Bence, K.K., Delibegovic, M., Xue, B., Gorgun, C.Z., Hotamisligil, G.S., Neel, B.G., Kahn, B.B., Neuronal PTP1B regulates body weight, adiposity and leptin action (2006) Nat Med, 12, pp. 917-924Boujendar, S., Reusens, B., Merezak, S., Ahn, M.T., Arany, E., Hill, D., Remacle, C., Taurine supplementation to a low protein diet during foetal and early postnatal life restores a normal proliferation and apoptosis of rat pancreatic islets (2002) Diabetologia, 45, pp. 856-866Carneiro, E.M., Latorraca, M.Q., Araujo, E., Beltra, M., Oliveras, M.J., Navarro, M., Berna, G., Martin, F., Taurine supplementation modulates glucose homeostasis and islet function (2009) J Nutr Biochem, 2008, pp. 1-9De Souza, C.T., Araujo, E.P., Bordin, S., Ashimine, R., Zollner, R.L., Boschero, A.C., Saad, M.J., Velloso, L.A., Short-term inhibition of peroxisome proliferator-activated receptor-gamma coactivator- 1alpha expression reverses diet-induced diabetes mellitus and hepatic steatosis in mice (2005) Endocrinology, 146, pp. 4192-4199El Idrissi, A., Boukarrou, L., L'Amoreaux, W.J., Taurine supplementation and pancreatic remodeling (2009) Adv Exp Med Biol, 643, pp. 353-358Heilbronn, L.K., Ravussin, E., Calorie restriction and aging: Review of the literature and implications for studies in humans (2003) Am J Clin Nutr, 78, pp. 361-369Kahn, S.E., Hull, R.L., Utzschneider, K.M., Mechanisms linking obesity to insulin resistance and type 2 diabetes (2006) Nature, 444, pp. 840-846Kalbe, L., Leunda, A., Sparre, T., Meulemans, C., Ahn, M.T., Orntoft, T., Kruhoffer, M., Remacle, C., Nutritional regulation of proteases involved in fetal rat insulin secretion and islet cell proliferation (2005) Br J Nutr, 93, pp. 309-316L'Amoreaux, W.J., Cuttitta, C., Santora, A., Blaize, J.F., Tachjadi, J., El Idrissi, A., Taurine regulates insulin release from pancreatic beta cell lines (2010) J Biomed Sci, 17 (SUPPL. 1), pp. S11. , 1-8Maturo, J., Kulakowski, E.C., Taurine binding to the purified insulin receptor (1988) Biochem Pharmacol 1, 37 (19), pp. 3755-3760Mollinedo, E.L., Millán, E.F., Santos, L.M., Honduvilla, C.J.M., Alvarez, C., Escrivá, F.J., Early undernutrition increases glycogen content and reduces the activated forms of GSK3, AMPK, p38 MAPK, and JNK in the cerebral cortex of suckling rats (2010) Neurochem, 112, pp. 123-133Morrison, A.B., Campbell, J.A., Evaluation of protein in foods. V. Factors influencing the protein efficiency ratio offoods (1960) J Nutr, 70, pp. 112-118Morton, G.J., Cummings, D.E., Baskin, D.G., Barsh, G.S., Schwartz, M.W., Central nervous system control offood intake and body weight (2006) Nature, 443, pp. 289-295Nardelli, T.R., Ribeiro, R.A., Balbo, S.L., Vanzela, E.C., Carneiro, E.M., Boschero, A.C., Bonfleur, M.L., Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamateobese rats (2011) Amino Acids Oct, 41 (4), pp. 901-908Orozco-Solís, R., Matos, R.J., Guzmán-Quevedo, O., Lopes De Souza, S., Bihouée, A., Houlgatte, R., Manhães De Castro, R., Bolaños-Jiménez, F., Nutritional programming in the rat is linked to long-lasting changes in nutrient sensing and energy homeostasis in the hypothalamus (2010) PLoS One, 5 (10), pp. e13537Petry, C.J., Dorling, M.W., Pawlak, D.B., Ozanne, S.E., Hales, C.N., Diabetes in old male offspring of rat dams fed a reduced protein diet (2001) Int J Exp Diabetes Res, 2, pp. 139-143Pirola, L., Johnston, A.M., Van Obberghen, E., Modulation of insulin action (2004) Diabetologia, 47, pp. 170-184Plum, L., Belgardt, B.F., Bruüning, J.C., Central insulin action in energy and glucose homeostasis (2006) J Clin Invest, 116, pp. 1761-1766Ribeiro, R.A., Batista, T.M., Coelho, F.M., Boschero, A.C., Lopes, G.S., Carneiro, E.M., Decreased beta-cell insulin secretory function in aged rats due to impaired Ca2+ handling (2012) Exp Physiol, 97 (9), pp. 1065-1073Romanatto, T., Cesquini, M., Amaral, M.E., Roman, E.A., Moraes, J.C., Torsoni, M.A., Cruz-Neto, A.P., Velloso, L.A., TNF-alpha acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient-effects on leptin and insulin signaling pathways (2007) Peptides, 28, pp. 1050-1058Schwartz Jr., M.W., Porte, D., Diabetes, obesity, and the brain (2005) Science, 307, pp. 375-379Schwartz, M.W., Woods, S.C., Porte Jr., D., Seeley, R.J., Baskin, D.G., Central nervous system control offood intake (2000) Nature, 404, pp. 661-671Snoeck, A., Remacle, C., Reusens, B., Hoet, J.J., Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas (1990) Biol Neonate, 57, pp. 107-118Solon, C., Franci, D., Souza, L.M.I., Romanatto, T., Roman, E.R., Arruda, A., Torsoni, A., Velloso, L., Taurine enhances the anorexigenic effects of insulin in the hypothalamus of rats (2012) Amino Acids, 42 (6), pp. 2403-2410Tsai, W.C., Bhattacharyya, N., Han, L.Y., Hanover, J.A., Rechler, M.M., Insulin inhibition of transcription stimulated by the forkhead protein Foxo1 is not solely due to nuclear exclusion (2003) Endocrinology, 144, pp. 5615-5622Tsuboyama-Kasaoka, N., Shozawa, C., Sano, K., Kamei, Y., Kasaoka, S., Hosokawa, Y., Ezaki, O., Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity (2006) Endocrinology, 147, pp. 3276-3284Zabolotny, J.M., Kim, Y.B., Welsh, L.A., Kershaw, E.E., Neel, B.G., Kahn, B.B., Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo (2008) J Biol Chem, 283, pp. 14230-1424
- …
