1,721,042 research outputs found
Differential p70S6k and 4E-BP1 regulation by insulin and amino acids in vascular endothelial and smooth muscle cells
No full textDifferential stimulation of vascular endothelial and smooth muscle cells proliferation is responsible for atherosclerotic lesions. Amino acids and insulin modulate p70S6k and 4E-BP1 activity, regulating cell growth and proliferation. We hypothesised that nutritional (amino acids) and hormonal (insulin) signals differently modulate protein anabolism in human vascular endothelial (HUVEC) and smooth muscle (HVSMC) cells. We evaluated p70S6kinase and 4E-BP1 phosphorylation in the two cell types, grown in amino acid-free medium with or without insulin (INS, 100 nM) or/and amino acids mixture (AA, 3 mM) and with the selective addition or deprivation of branched chain amino acids (BCAA, 0.5 mM). INS stimulated p70S6k and 4E-BP1 phosphorylation transiently in HUVEC and persistently in HVSMC. AA and INS+AA stimulated p70S6k and 4E-BP1 phosphorylation persistently in HUVEC and HVSMC. AA, but not BCAA alone or BCAA-deprived AA, induced p70S6k phosphorylation in HUVEC. BCAA deprivation decreased the p70S6k phosphorylation induced by AA with or without insulin in HVSMC. These results show that anabolic stimuli modulate p70S6k and 4E-BP1 activity differently in the two vascular cell types, suggesting that insulin stimulates protein synthesis for a longer time in HUSMC than in HUVEC. We speculate that hyperinsulinaemia frequently associated with atherosclerosis could induce a selective HVSMC proliferation
Sugars, exercise and health
Full text linkBackground: There is a direct link between a variety of addictions and mood states to which exercise could be relieving. Sugar addiction has been recently counted as another binge/compulsive/addictive eating behavior, differently induced, leading to a high-significant health problem. Regularly exercising at moderate intensity has been shown to efficiently and positively impact upon physiological imbalances caused by several morbid conditions, including affective disorders. Even in a wider set of physchiatric diseases, physical exercise has been prescribed as a complementary therapeutic strategy. Method: A comprehensive literature search was carried out in the Cochrane Library and MEDLINE databases (search terms: sugar addiction, food craving, exercise therapy, training, physical fitness, physical activity, rehabilitation and aerobic). Results: Seeking high-sugar diets, also in a reward- or craving-addiction fashion, can generate drastic metabolic derangements, often interpolated with affective disorders, for which exercise may represent a valuable, universal, non-pharmachological barrier. Limitations: More research in humans is needed to confirm potential exercise-mechanisms that may break the bond between sugar over-consumption and affective disorders. Conclusions: The purpose of this review is to address the importance of physical exercise in reversing the gloomy scenario of unhealthy diets and sedentary lifestyles in our modern society
Antropometry in HIV patients: effects of recombinant human growth hormone
No full textAbstract Patients with HIV infection treated with protease inhibitors (PIs) drugs for a long period have a prolonged life expectancy and an improvement of quality of life. Often, HIV-patients on PIs
develop a syndrome characterized by peripheral lipoatrophy, truncal fat accumulation, hyperlipemia and insulin resistance. In HIV-1 patients undergoing antiretroviral treatment, lipodystrophy is associated with peripheral fat wasting and central adiposity, dyslipidemia, insulin resistance, and increased intramuscular fat accumulation.
In HIV lipodystrophy fat distribution changes are heterogeneous and can include reduced subcutaneous fat and increased visceral fat. In literature there are evidences showing overnight growth
hormone (GH) secretion and pulse amplitude reduction in patients with HIV lipodystrophy, in response to standard GH stimulation test. Excess accumulation of visceral fat with increasing of intra-abdominal adiposity (central obesity) is also a typical feature of patients with GH deficiency. Recombinant human growth hormone (rhGH) can be a useful treatment to diminish excess visceral fat. Up to day there are evidences that GH therapy in HIV-infected patients with syndromes of central fat accumulation show a significant decrease of body fat. In this chapter, we discuss the anthropometry of lipodystrophy in HIV patients and the indication of rhGH treatment in HIV-related lipodystrophy
Are genetic variants of the methyl group metabolism enzymes risk factors predisposing to obesity?
No full textObesity, due to the combination of inherited genes and environmental factors, is continually increasing. We evaluated the relationship between polymorphisms of methylene-tetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), betaine:homocysteine methyltransferase (BHMT G742A) and cystathionine beta-synthase (CBS 68-bp ins) genes and the risk of obesity. We studied these polymorphic variants in 54 normal and 82 obese subjects [body mass index (BMI)=22.4+/-1.8, 34.1+/-7.1; ages 35.2+/-10.7, 43.3+/-10.6 respectively]. Levels of total plasma homocysteine (t-Hcy), folates, and vitamins B6 and B12 were not significantly different, while leptin concentration was significantly higher (p=0.005) in the obese patients compared to the lean controls. The frequency of only (a) MTHFR (AC), (b) MTR (AG), and (c) MTRR (AG) heterozygous genotypes was statistically different in the obese compared to the control group (p=0.03, p=0.007, and p=0.01). Single (a), (b), and (c) heterozygous genotypes had a significant risk of developing obesity [p=0.02, 0.01, and 0.03; odds ratio (OR)=2.5, 3.0, and 2.4; 95% confidence interval (CI)=1.2-5.3, 1.3-7.1, and 1.2-5.1 respectively] and the risk remarkably increased for combined genotypes a+b, a+c, b+c, and a+b+c (p=0.002, 0.002, 0.016, 0.006; OR=7.7, 5.4, 5.8, 15.4; 95% CI=1.9-30.4, 1.7-16.8, 1.4-23.2, 1.6- 152.3). These findings suggest that in obese subjects, Hcy cycle efficiency is impaired by MTHFR, MTR, and MTRR inability to supply methyl-group donors, providing evidence that MTHFR, MTR, and MTRR gene polymorphisms are genetic risk factors for obesity
Potential therapeutic role of L-carnitine in skeletal muscle oxidative stress and atrophy conditions
Full text linkThe targeting of nutraceutical treatment to skeletal muscle damage is an emerging area of research, driven by the need for new therapies for a range of muscle-associated diseases. L-Carnitine (CARN) is an essential nutrient and plays a key role in mitochondrial β-oxidation and in the ubiquitin-proteasome system regulation. As a dietary supplement to improve athletic performance, CARN has been studied for its potential to enhance β-oxidation. However, CARN effects on myogenesis, mitochondrial activity, and hypertrophy process are not completely elucidated. This in vitro study aims to investigate CARN role on skeletal muscle remodeling, differentiation process, and myotubes formation. We analyzed muscle differentiation and morphological features in C2C12 myoblasts exposed to 5 mM CARN. Our results showed that CARN was able to accelerate C2C12 myotubes formation and induce morphological changes, characterizing the start of hypertrophy process. In addition, CARN improved AKT activation and downstream cellular signaling pathways involved in skeletal muscle atrophy process prevention. Also, CARN positively regulated the pathways involved in oxidative stress defense. In this work, we provide an interesting novel mechanism of the potential therapeutic use of CARN to treat pathological conditions characterized by skeletal muscle morphological and functional impairment, oxidative stress production, and atrophy process in aging
Glucose and leucine metabolism in lung tranplanted patients on low dose of steroids for immunosuppressive therapy
No full textThis study examined the metabolic effects of lung transplantation in patients with end-stage respiratory failure on low dose of steroids for immunosuppressive therapy. METHODS: We examined 6 patients, including 2 women and 4 men of overall mean age 53 +/- 15 years and age at transplantation 34 +/- 12 months, receiving cyclosporine 5.73 +/- 1.43 mg/kg/d or tacrolimus (FK 506) 4.67 +/- 0.58 mg/d, azathioprine 0.47 +/- 0.29 mg/kg/d, and prednisone 8.25 mg/d for comparison with 6 healthy subjects, who were selected to be comparable to the recipients in terms of anthropometric features and age. A euglycemic hyperinsulinemic clamp (1 mU/kg/min) associated with infusion of glucose and leucine isotopes was performed with indirect calorimetry. RESULTS: Lung transplanted patients showed postabsorptive leucine and free fatty acid metabolism similar to controls. In contrast, there was peripheral insulin resistance with respect to glucose metabolism namely, higher values of glucose and insulin vs controls (P < .03 and P < .02, respectively). During the clamp the metabolic picture was characterized by a relative insulin resistance with respect to glucose metabolism (P = .07). Lipid and protein metabolism in the basal and insulin-stimulated conditions were similar to the control group. CONCLUSIONS: In the basal condition insulin resistance is evident with respect to glucose metabolism. The metabolic picture in lung transplanted patients on low-dose steroid therapy was characterized by normal insulin-stimulated glucose, leucine, and free fatty acid metabolism. The minimal metabolic alterations in these patients were not due to transplantation itself but probably mainly attributable to immunosuppressive therap
Recombinant human growth hormone : rationale for use in the treatment of HIV-associated lipodystrophy
No full textThe role of hormonal and metabolic alterations in HIV-associated lipodystrophy syndrome is not yet clear. In patients with HIV-1 undergoing antiretroviral treatment, lipodystrophy is associated with peripheral fat wasting and central adiposity, dyslipidemia, insulin resistance, and increased intramuscular fat accumulation. In HIV lipodystrophy, changes in fat distribution are heterogeneous and can include reduced subcutaneous fat as well as increased visceral fat. In the literature, there is evidence showing that overnight growth hormone (GH) secretion and pulse amplitude decrease in patients with HIV lipodystrophy, with rates of response to standardized GH stimulation being abnormal in at least 20% of these patients. Excess accumulation of visceral fat, central obesity, and increased intra-abdominal adiposity are also typical features of patients with GH deficiency. Recombinant human GH (rhGH) is a potential treatment to diminish excess visceral fat. Our group recently demonstrated that GH therapy in HIV-infected patients with syndromes of fat accumulation produced a significant decrease in body fat and a gain in lean tissue. In this article, we discuss the origin of lipodystrophy in HIV patients, and the use of rhGH treatment (benefits and adverse effects) in HIV-related lipodystrophy
Immunosuppressive therapy in pancreas and islet transplant : Need for simultaneous assessment of insulin sensitivity and secretion
Full text linkDiabetes mellitus is a metabolic disease possi- ble to treat via pancreas/islet transplantation but most immunosuppressive drugs are diabeto- genic. In this letter, we review current up to date methods to assess insulin action and secretion (using the surrogate indexes) suggesting their use in large studies in populations of pancreas/ islets transplanted patients
Modulation of cell cycle progression by 5-azacytidine is associated with early myogenesis induction in murine myoblasts
Full text linkMyogenesis is a multistep process, in which myoblasts withdraw from the cell cycle, cease to divide, elongate and fuse to form multinucleated myotubes. Cell cycle transition is controlled by a family of cyclin-dependent protein kinases (CDKs) regulated by association with cyclins, negative regulatory subunits and phosphorylation. Muscle differentiation is orchestrated by myogenic regulatory factors (MRFs), such as MyoD and Myf-5. DNA methylation is crucial in transcriptional control of genes involved in myogenesis. Previous work has indicated that treatment of fibroblasts with the DNA-demethylating agent 5-azacytidine (AZA) promotes MyoD expression. We studied the effects of AZA on cell cycle regulation and MRFs synthesis during myoblast proliferation and early myogenesis phases in C2C12 cells. During the proliferation phase, cells were incubated in growth medium with 5μM AZA (GMAZA) or without AZA (GM) for 24 hours. At 70% confluence, cells were kept in growth medium in order to spontaneously achieve differentiation or transferred to differentiation medium with 5μM AZA (DMAZA) or without AZA (DM) for 12 and 24 hours. Cells used as control were unstimulated. In the proliferation phase, AZA-treated cells seemed to lose their characteristic circular shape and become elongated. The presence of AZA resulted in significant increases in the protein contents of Cyclin-D (FC:1.23 GMAZA vs GM p≤0.05), p21 (FC: 1.23 GMAZA vs GM p≤0.05), Myf-5 (FC: 1.21 GMAZA vs GM p≤0.05) and MyoD (FC: 1.20 GMAZA vs GM p≤0.05). These results propose that AZA could inhibit cell proliferation. During 12 hours of differentiation, AZA decreased the downregulation of genes involved in cell cycle arrest and in restriction point (G1 and G1/S phase) and the expression of several cyclins, E2F Transcription Factors, cyclin-dependent kinase inhibitors, specific genes responsible of cell cycle negative regulation. During 24 hours of differentiation, AZA induced an increment in the protein expression of Myf-5 (FC: 1.57 GMAZA vs GM p≤0.05), MyoD (FC: 1.14 DM vs GM p≤0.05; FC: 1.47 DMAZA vs GM p≤0.05), p21 (FC: 1.36 GMAZA vs GM p≤0.01; FC: 1.49 DM vs GM p≤0.05; FC: 1.82 DMAZA vs GM p≤0.01) and MyHC (FC: 1.40 GMAZA vs GM p≤0.01; FC: 2.39 DM vs GM p≤0.05; FC: 3.51 DMAZA vs GM p≤0.01). Our results suggest that AZA-induced DNA demethylation can modulate cell cycle progression and enhance myogenesis. The effects of AZA may open novel clinical uses in the field of muscle injury research and treatment
In human endothelial cells amino acids inhibit insulin-induced Akt and ERK1/2 phosphorylation by an mTOR-dependent mechanism
No full textIn several cellular systems, amino acids synergize with insulin in promoting protein synthesis through the activation of the protein kinases p70/S6-K and PHAS-1. Such activations are mediated by the upstream kinase: mammalian target of rapamycin (mTor).In this work we have investigated the intracellular pathways involved in insulin-induced and amino acid-induced p70/S6-K activations in human endothelial cells.In human umbilical vein endothelial cells, insulin induces the phosphorylation of p70/S6-K at 5 minutes decreasing thereafter, whereas amino acids alone or associated with insulin phosphorylate p70/S6-K at all the time points analyzed (60 minutes). Insulin and amino acids phosphorylate p70/S6-K by mTor-dependent and phosphotidylinositol 3-kinase-dependent mechanisms, whereas the mitogen-activated protein kinase pathway is involved only when p70/S6-K is activated by insulin.Insulin induces the phosphorylation of Akt and extracellular signal-regulated protein kinase (ERK) 1/2, whereas amino acids did not. Moreover, amino acids suppress the phosphorylations induced by insulin. The inhibitory effects of amino acids are reverted by the mTor inhibitor rapamycin.Insulin-induced phosphorylation of Akt (at 15 and 30 minutes) is not accompanied by the phosphorylation of the downstream kinase p70/S6-K, indicating the existence of a negative feedback at this level.Our data demonstrate that at the level of human endothelial cells, amino acids synergize with insulin in the phosphorylation of the kinase that lies downstream mTor, as p70/S6-K, whereas they inhibit the upstream kinases Akt and extracellular signal-regulated protein kinase 1/2 when activated by insulin, by an mTor-dependent mechanism. Copyright (copyright) 2006 by Lippincott Williams & Wilkins
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