Study on Microcirculation in Islets of Langerhans

1.大鼠胰岛血流量的测定由于胰岛广泛分布于胰腺内，故采用彩色微球法测量胰岛血流量。虽然在以前的研究中使用了单一颜色的微球，但我开发了一种新的方法来测量不同时间点的胰岛血流量，使用不同颜色的微球。不同年龄肥胖2型糖尿病OLETF大鼠胰岛血流量的变化OLETF大鼠胰岛血流量较对照组增加一倍，且在肥胖或高血糖发生之前，胰岛血流量在较年轻时即可观察到。然而，在通过蔗糖喂养加重高血糖后，这种增加变得不明显，而在通过限制饮食防止肥胖的发展之后，这种增加是增加的。给幼年OLETF大鼠应用一氧化氮合酶抑制剂后，胰岛血流量不再增加。这提示OLETF大鼠胰岛血液过度灌流可能是通过NO依赖机制介导的。CCK对胰岛血流量的影响CCK既有促胰岛素作用，又有刺激胰腺外分泌的作用。CCK通过CCK-A受体而不是迷走神经机制介导的非依赖性机制增加胰岛血流量。那格列奈对胰岛血流的影响那格列奈是一种速效胰岛素促分泌剂，最近进入临床应用。那格列奈可显著增加胰岛血流量，而甲苯丁胺无此作用。清醒大鼠胰岛血流量及胰岛素诱导的降糖效应建立了一种测量非麻醉大鼠胰岛血流量的新方法。麻醉影响胰腺内的血流分布，迷走神经通路阻止低血糖时胰岛血流量的增加。

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.