Browsing by Subject "Insulin"
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Item Calcium Sensitivy of β-cell Transcription Factor Binding to an Insulin Enhancer(1998-06-01) Scott, Gary Frank; Easom, Richard; Lacko, Andras G.; Wu, Ming-ChiGary Frank Scott, Calcium Sensitivity of β-cell Transcription Factor Binding to an Insulin Enhancer. Master of Science (Biochemistry and Molecular Biology), June 1998, 104 pp., 16 illustrations, bibliography, 94 titles. Insulin is an essential hormone and is produced exclusively in endocrine pancreas β-cells for the control of glucose homeostasis in mammals. The hypothesis tested in this thesis is that increased intracellular Ca2+ ([Ca2+]i) contributes to activation of glucose-induced insulin gene transcription. Glucose-induced insulin transcription has been mapped to binding of transcription factors by β-cell sequence motifs from -197 to -247, a glucose-response-enchancer (GRE), in the rat insulin1 gene (rINS1) promoter. Using oligonucleotide probes representing this glucose-response-enhancer (GRE) in electrophorectic mobility shift assays (EMSA), we have examined the Ca2+-sensitivity of transcription factor binding to nuclear extracts from cultured rat insulinoma β-cells (INS-1). In the presence or absence of kinase inhibitors, Ca2+ chelators, and Ca2+ channel blockers, binding was assayed for the following cell conditions: 1) in situ permeabilized cells exposed to Ca2+; 2) in vitro 32p-phosphorylated nuclear extracts; and 3) in situ glucose-stimulated and K+-depolarized intact cells. Binding was Ca2+-sensitive due to activation by K+depolarization as well as inhibition by a Ca2+-chelator, a Ca2+-channel blocker, and KN-93, specific for Ca2+/calmodulin kinases, suggesting a phosphorylation-dependent mechanism. Taken together, these findings identify a role for the Ca2+ second messenger in the glucose regulation of the insulin gene which points to novel treatments for type II diabetes.Item SUSTAINED CHANGES IN GLP-1 AND INSULIN 12 MONTHS AFTER LAPAROSCOPIC GASTRIC BANDING SURGERY(2014-03) Ake, Stephen; Franks, Susan; Smith, Adam B.Bariatric surgery has been effective in promoting sustained weight loss and improving diabetes control in many patients with morbid obesity. Increases in GLP-1 after bariatric surgery have been implicated in improved glucose homeostasis in studies examining Roux-en-Y gastric bypass. However similar studies in laparoscopic gastric banding surgery (LGBS) have been conflicting. The co-authors of the present study previously reported an increase in GLP-1 and a decrease in insulin 6 months after LGBS. The aim of this study was to further evaluate sustained changes in GLP-1 and insulin after LGBS. Purpose (a): The following hypotheses were examined: (1) Fasting and post-prandial (pp) GLP-1 will be increased 12 months after LGBS, and (2) Fasting and pp-insulin will be decreased after LGBS. Relationships between GLP-1 and weight loss were explored. Methods (b): Thirteen LGBS patients (9 women and 4 men) who underwent pre-surgical and 6-month post-surgical testing were retested at 12-months post-surgically. Average baseline BMI was 40.5 (32.4-48.4). Average age was 47.5 (24-66). Fasting and pp-blood samples were taken to evaluate GLP-1 and insulin. Data were analyzed using repeated measures ANOVA. Results (c): In comparison to baseline, fasting GLP-1 increased (F=6.46, p=0.006), fasting insulin decreased (F=6.11, p=0.022) and pp-insulin decreased (F=9.46, p=0.008). The ppGLP-1 increase approached significance (F=3.70, p=0.065), with a significant post-hoc pairwise finding at 12-months in comparison to baseline (p=0.004). Conclusions (d): Results suggest that LGBS improves GLP-1 and insulin as early as 6 months and that these improvements persist up to 1 year. Overall, these improvements appear independent of weight loss, although exploration of data suggests a possible connection with post-prandial GLP-1 at 12-months. These results provide further evidence of the efficacy of LGBS for the treatment of diabetes.Item The Effects of Insulin on Myocardial Glucose Metabolism and Contractile Function During Moderate Coronary Hypoperfusion(1997-08-01) Tune, Johnathan D.; Downey, H. Fred; Mallet, Robert T.; Caffrey, James L.Tune, Jonathan David, The Effects on Insulin on Myocardial Glucose Metabolism and Contractile Function during Moderate Coronary Hypoperfusion Doctor of Philosophy (Biomedical Sciences), August, 1997, 98 pp, 3 tables, 11 figures, references, 117 titles. This study was designed to determine the effects of insulin on myocardial metabolism and contractile function during moderate coronary hypoperfusion. Coronary perfusion pressure (CPP) was lowered from 100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery of anesthetized, open chest dogs. Regional glucose uptake, lactate uptake, oxygen consumption (MVO2), and percent segment shortening were determined without (n=12) or with either intravenous insulin (4 U/min, n=12) or intracoronary insulin (4 U/min, n=6). Glucose metabolites, high energy phosphates, and the phosphorylation state of creatine phosphate were determine in freeze clamped biopsies of control (n=6), and of intravenous insulin (n=6) treated hearts at the completion of the protocol (CPP = 40 mmHg). Glucose uptake increased with both intravenous and intracoronary insulin treatments (P0.05). Thus, insulin treatment improved contractile function while myocardial oxygen demand was unchanged, i.e. oxygen utilization efficiency increased. Myocardial glycogen, alanine, lactate, and pyruvate contents were not significantly different in untreated and intravenous insulin treated hearts. Reducing CPP to 40 mmHg produced similar changes in both untreated and insulin treated hearts: ATP content was unchanged, creatine phosphate content decreased 17%, creatine content and inorganic phosphate concentration increased 27% and 124%, respectively, and the phosphorylation potential decreased 80%. We conclude that 1) when the potentially detrimental effects on insulin stimulated glucose metabolism are avoided during moderate ischemia, insulin treatment increases contractile function without significantly elevating myocardial oxygen demand; 2) during moderate ischemia, insulin stimulated glucose metabolism increases oxygen utilization efficiency and prevents a further decline in the energy state of the myocardium.