2,611 research outputs found

    Glucokinase activity in isolated islets from obese fa/fa Zucker rats

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    Glucokinase (EC 2.7.1.2) activity of B-cells was measured in extracted pancreatic islets isolated from lean and obese fa/fa Zucker rats and maintained in primary culture overnight. Formation of [14C]glucose phosphoric esters from D-[U-14C]glucose was measured in the presence of unlabelled glucose from 0.05 to 0.50 mM for hexokinase (EC 2.7.1.1) activity, and 8.0-16.0 mM unlabelled glucose for glucokinase activity. Eadie-Hofstee analysis revealed that hexokinase kinetic parameters (Vmax and Km) for [14C]glucose phosphoric ester formation were similar in lean- and fa/fa-rat islets. For glucokinase, there was no difference in Vmax. between phenotypes. A non-significant tendency to increased sensitivity to glucose was noted in the fa/fa-rat islets (P = 0.13). In lean-rat islets, the glucokinase inhibitor mannoheptulose (3 mM) decreased Vmax. by 80% and increased the apparent Km from 3.3 +/- 0.7 mM to 12.2 +/- 2.0 mM (P < 0.05). There was no difference in Km or Vmax. in mannoheptulose-treated versus control islets from fa/fa rats. This lack of effect was consistent with reported effects of mannoheptulose on insulin secretion from fa/fa-rat islets [Chan, MacPhail and Mitton (1993) Can. J. Physiol. Pharmacol. 71, 34-39]. The data from glucose and mannoheptulose experiments support the hypothesis that glucokinase function is altered in fa/fa Zucker rats and may contribute to fasting hyperinsulinaemia in vivo in these animals.LR: 20061115; PUBM: Print; JID: 2984726R; 11061-68-0 (Insulin); 654-29-5 (Mannoheptulose); EC 2.7.1.1 (Hexokinase); EC 2.7.1.2 (Glucokinase); ppublishSource type: Electronic(1

    Relationship between objective measures of physical activity and weather: a longitudinal study

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    Background The weather may be a barrier to physical activity but objective assessment of this hypothesis is lacking. Therefore we evaluated the effect of temperature, rain or snow, and wind speed on the daily physical activity of adults. Methods This report contains data from 25 males (BMI (mean ± SD): 28.7 ± 3.83 kg/m2) and 177 females (BMI: 29.2 ± 5.92 kg/m2) enrolled in an intervention to increase physical activity. Steps/day of the participants was measured by pedometer. Weather data were obtained from Environment Canada. A total of 8,125 observations were included in a mixed linear model analysis. Results Significant weather related variables (at the 5% level) impacting steps/day included: seasonal effects related to the interaction between weekday and month; mean temperature, total rainfall, interactions between gender, BMI and total snow, interactions between maximum wind speed and BMI, and the amount of snow on the ground. The estimated magnitudes for the various effects were modest, ranging from ~1% to ~20%. Thus for an average individual taking ~10,000 steps/day, weather-dependent changes in physical activity could reach 2,000 steps/day. Conclusion We conclude that weather had modest effects on physical activity of participants in an intervention to increase their activity. It should be stressed that these effects may be different for less or more motivated people. With this in mind, we suggest that the effect of weather on physical activity in the general population needs to be objectively assessed to better understand the barrier it poses, especially as it relates to outdoor recreation or work activities.</p

    Transcriptional regulation of lipid metabolism by fatty acids: a key determinant of pancreatic β-cell function

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    Abstract Background Optimal pancreatic β-cell function is essential for the regulation of glucose homeostasis in both humans and animals and its impairment leads to the development of diabetes. Type 2 diabetes is a polygenic disease aggravated by environmental factors such as low physical activity or a hypercaloric high-fat diet. Results Free fatty acids represent an important factor linking excess fat mass to type 2 diabetes. Several studies have shown that chronically elevated free fatty acids have a negative effect on β-cell function leading to elevated insulin secretion basally but with an impaired response to glucose. The transcription factors PPARα, PPARγ and SREBP-1c respond to changing fat concentrations in tissues, thereby coordinating the genomic response to altered metabolic conditions to promote either fat storage or catabolism. These transcription factors have been identified in β-cells and it appears that each may exert influence on β-cell function in health and disease. Conclusion The role of the PPARs and SREBP-1c as potential mediators of lipotoxicity is an emerging area of interest.</p

    Functional characterization of alpha-adrenoceptors on pancreatic islets of fa/fa Zucker rats

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    Recently, a defect in pertussis toxin-independent actions of epinephrine on pancreatic B-cells of fa/fa Zucker rats was reported (Cawthorn and Chan (1991) Mol. Cell. Endocrinol. 75, 197-204). We now report studies of islet alpha 2-adrenoceptor function of fa/fa rats. Insulin and cAMP production by islets of obese rats were both inhibited by the alpha 2-adrenoceptor agonist clonidine. Calculated pD2 values for clonidine were 9.57 +/- 0.59 and 9.43 +/- 0.33 for lean and fa/fa rat islets, respectively. Yohimbine reversed clonidine effects equipotently in lean and obese rat islets (pA2 values of 7.48 +/- 0.57 vs 7.43 +/- 0.58). Unexpectedly, the alpha 1-antagonist prazosin stimulated insulin secretion from islets of obese but not lean rats. Functional characteristics of the alpha-adrenoceptors on fa/fa islets are thus similar to those recently designated alpha 2B. Altered expression of alpha-adrenoceptors on pancreatic islets of fa/fa rats may contribute to changes in the pertussis toxin-independent pathway of epinephrine action previously observed.LR: 20061115; PUBM: Print; JID: 7500844; 0 (Receptors, Adrenergic, alpha); 11061-68-0 (Insulin); 146-48-5 (Yohimbine); 19216-56-9 (Prazosin); 4205-90-7 (Clonidine); 50-99-7 (Glucose); 51-43-4 (Epinephrine); 60-92-4 (Cyclic AMP); 66428-89-5 (Forskolin); ppublishSource type: Electronic(1

    Paravertebral Blockade of the Brachial Plexus in Dogs

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    Kip A. Lemke, Catherine M. Creighto

    Interactions between effects of adrenalectomy and diet on insulin secretion in fa/fa Zucker rats

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    Our objective was to determine if a cafeteria-type diet with increased fat content would block the decrease in insulin secretion induced by adrenalectomy in obese rats. Five week old Zucker (fa/fa) rats were adrenalectomized. One week later, half of the adrenalectomized groups, and age-matched, sham-operated animals were given a diet of 16% fat and 44% carbohydrate. Control animals were maintained on standard rat chow (4.6% fat and 49% carbohydrate). After 4 weeks on the diets, in vivo measurements included caloric intake, weight gain, plasma corticosterone, triglyceride, free fatty acids, and oral glucose tolerance tests. In vitro measurements included glucose-stimulated insulin secretion, glucose phosphorylating activity, islet triglyceride content, and fatty acid oxidizing activity of cultured islets. Generally, the cafeteria diet did not block the effects of adrenalectomy on in vitro insulin secretion parameters, even though in sham-operated animals weight gain and insulin resistance was induced by the diet in vivo. Adrenalectomy and the diet exerted independent effects on glucose phosphorylation and fatty acid oxidation in islets. In conclusion, adrenalectomy decreased the elevated insulin secretion in fa/fa rats. The failure of a cafeteria diet enriched in fat to block the adrenalectomy-mediated changes in B-cell function indicates the importance of glucocorticoids and centrally-mediated effects on insulin secretion and other metabolic parameters.LR: 20061115; PUBM: Print; JID: 0372712; 0 (Dietary Fats); 0 (Fatty Acids, Nonesterified); 0 (Triglycerides); 11061-68-0 (Insulin); 50-22-6 (Corticosterone); EC 2.7.1.2 (Glucokinase); ppublishSource type: Electronic(1

    Numerical-simulation of plasma processes driven by tranverseI on heating

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    PT: JSource type: Electronic(1

    Effect of somatostatin on intragastric pressure and smooth muscle contractility of the rainbow trout, Oncorhynchus mykiss Walbaum

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    Isolated vascularly-perfused stomach and strips of gastrointestinal smooth muscle of rainbow trout were suspended in solutions containing somatostatin. In stomach, somatostatin 10-1000 nM decreased maximum and baseline intragastric pressure by 10-20% in the presence of stimulatory doses of carbachol or 5-hydroxytryptamine. Somatostatin 1 micro M inhibited by 50% the magnitude of spontaneous contractions generated by distension. Somatostatin had little effect on the pressure gradient or contractile frequency. Results suggest that somatostatin may negatively modulate gastric emptying in rainbow trout. In gastric smooth muscle, somatostatin 100 pmol inhibited tension stimulated by carbachol (circular orientation of muscle) or 5-hydroxytryptamine (longitudinal orientation). These results correlated with those observed in stomach. Somatostatin also decreased tension stimulated by carbachol and 5-hydroxytryptamine in intestinal smooth muscle, suggesting that under some conditions somatostatin could increase gastric emptying rate by relaxing intestinal musculature..RE: 20 ref.; RN: 51110-01-1; SC: BE; CA; ZA; 0NSource type: Electronic(1

    Effects of equatorially trapped ions on refilling of the plasmasphere

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    PT: JSource type: Electronic(1

    Glucose-regulated glucagon secretion requires insulin receptor expression in pancreatic alpha-cells

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    The insulin receptor (IR) and its signaling appear to be essential for insulin secretion from pancreatic beta-cells. However, much less is known about the role of the IR in alpha-cells. To assess the role of the IR in glucagon and insulin secretion, we engineered adeno-viruses for high efficiency small interference RNA (siRNA)-IR expression in isolated mouse pancreatic islets and lentiviruses for siRNA-IR expression in pancreatic alpha- and beta-cell lines (alpha-TC6 and MIN6) with specific, long term stable IR knockdown. Western blot analysis showed that these strategies resulted in 60-80% reduction of IR protein in islets and alpha- and beta-cell lines. Cell growth was reduced by 35-50% in alpha-TC and MIN6 cells stably expressing siRNA-IR, respectively. Importantly, glucagon secretion, in response to glucose (25 to 2.8 mm), was completely abolished in islets expressing siRNA-IR, whereas secretion increased 1.7-fold in islets expressing control siRNA. In contrast, there was no difference in glucose-stimulated insulin secretion when comparing siRNA-IR and siRNA control, with both groups showing a 1.7-fold increase. Islet glucagon and insulin content were also unaffected by IR knockdown. To further explore the role of the IR, siRNA-IR was stably expressed in pancreatic cell lines, which dramatically suppressed glucose-regulated glucagon secretion in alpha-TC6 cells (3.4-fold) but did not affect GSIS in MIN6 cells. Defects in siRNA-IR-expressing alpha-cells were associated with an alteration in the activity of Akt and p70S6K where insulin-induced phosphorylation of protein kinase B/AKt was greatly reduced while p70S6K activation was enhanced, suggesting that the related pathways play important roles in alpha cell function. This study provides direct evidence that appropriate expression of the IR in alpha-cells is required for glucose-dependent glucagon secretion.LR: 20061115; PUBM: Print-Electronic; DEP: 20050714; JID: 2985121R; 0 (RNA, Small Interfering); 11061-68-0 (Insulin); 147336-22-9 (Green Fluorescent Proteins); 50-99-7 (Glucose); 9007-92-5 (Glucagon); EC 2.7.1.112 (Receptor, Insulin); 2005/07/14 [aheadofprint]; ppublishSource type: Electronic(1
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