Study on Microcirculation in Islets of Langerhans

朗格汉斯岛微循环的研究

• 批准号: 11671128
• 负责人: IWASE Masanori
• 金额: $ 2.37万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671128/
• 关键词: Diabetes mellitus; Islets of Langerhans; Microcirculation; Diabetic models; Cholecystokinin; Oral hypoglycemic agents; Anesthesia; Hypoglycemia; 一酸化窒素; マイクロフェア; 局所血流量; ラット; マイクロスフェア; 消化管ホルモン; 迷走神経; 膵臓; モデル動物; インスリン; 肥満

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.

1. 测量大鼠胰岛血流由于胰岛在胰腺内分布广泛，因此采用彩色微球法测量胰岛血流。虽然以前的研究使用的是单一颜色的微球，但我开发了一种新的方法，可以使用不同颜色的微球来测量不同时间点的胰岛血流量。肥胖型2型糖尿病模型，不同年龄OLETF大鼠的胰岛血流量比对照组增加了2倍，并且在发生肥胖或高血糖之前的较年轻年龄观察到胰岛血流量的增加。然而，在通过蔗糖喂养加剧高血糖后，这种增加变得不明显，而在通过限制食物来防止肥胖的发展后，这种增加得到了加强。年轻OLETF大鼠给予一氧化氮合酶抑制剂后，胰岛血流量不再增加。这提示OLETF大鼠胰岛血高灌注可能通过no依赖机制介导。胆囊收缩素（CCK）对胰岛血流的影响CCK具有促胰岛素作用，并刺激胰腺外分泌。CCK通过CCK- a受体增强胰岛血流量，该机制由NO依赖机制介导，而非迷走神经机制。那格列奈是一种速效胰岛素促分泌剂，最近被引入临床实践。那格列奈急性增加胰岛血流量，而甲苯丁胺没有这种效果。清醒大鼠胰岛血流量及胰岛素对低血糖的影响建立了一种测量未麻醉大鼠胰岛血流量的新方法。麻醉影响胰腺内血流分布，迷走神经通路阻止低血糖时胰岛血流增加。

项目成果

M.Iwase: "Pancreatic islet blood flow in conscious rats during hyperglycemia and hypoglycemia"American Journal of Physiology. 280. R1601-R1605 (2001)

M.Iwase：“高血糖和低血糖期间清醒大鼠的胰岛血流量”美国生理学杂志。

M. Iwase: "Pancreatic islet blood flow in conscious rats during hyperglycemia and hypoglycemia"American Journal of Physiology. 280. R1601-R1605 (2001)

M. Iwase：“高血糖和低血糖期间清醒大鼠的胰岛血流”美国生理学杂志。