Study on Microcirculation in Islets of Langerhans

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1. Measurement of islet blood flow in ratsSince pancreatic islets are widely distributed within the pancreas, a color microsphere method has been adopted for the measurement of islet blood flow. Although a single colored microsphere was used in previous studies, I developed a new method to measure islet blood flow at different time points using different colors of microsphere.2. Islet blood flow in a model of obese type 2 diabetes mellitus, OLETF rats at different agesIslet blood flow was increased by twice in OLETF rats as compared to control, and the increase of islet blood flow was observed at younger age before the development of obesity or hyperglycemia. However, the increase became obscure after worsening hyperglycemia by sucrose feeding, whereas the increase was enhanced after preventing the development of obesity by food restriction. When nitric oxide (NO) synthase inhibitor was administered to young OLETF rats, islet blood flow was no more increased. This suggests that the islet blood hyperperfusion seen in OLETF rats may be mediated by NO-dependent mechanism.3. Effects of cholecystokinin(CCK) on islet blood flowCCK has insulinotropic effect as well as stimulates pancreatic exocrine secretion. CCK enhanced islet blood flow via CCK-A receptors, mediated by NO dependent mechanism, but not by vagal mechanism.4. Effects of nategfinide on islet blood flowNateglinide is a rapid-acting insulin secretagogue, recently introduced to clinical practice. Nateglinide acutely increased islet blood flow, whereas tolbutamide did not have such a effect.5. Islet blood flow in conscious rats and effect of insulin-induced hypoglycemiaI developed a new method to measure islet blood flow in unanesthetized rats. Anesthesia affected blood flow distribution within the pancreas, and vagal pathway prevented the increase of islet blood flow during hypoglycemia.