Ito K, Hirose H, Maruyama H, Fukamachi S, Tashiro Y, Saruta T
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Diabetologia. 1995 Nov;38(11):1276-84. doi: 10.1007/BF00401759.
To elucidate the mechanisms of insensitivity of hormone secretion to glucose in streptozotocin-induced diabetic rat islets, we investigated the effects of acetylcholine (ACh) and norepinephrine on insulin and glucagon secretion in response to changes in glucose concentration, using perfused pancreas preparations. Basal insulin secretion at a blood glucose level of 5.6 mmol/l was significantly higher and basal glucagon secretion significantly lower in streptozotocin-induced diabetic rats than in controls, and neither high (16.7 mmol/l) nor low (1.4 mmol/l) blood glucose concentrations influenced insulin or glucagon secretion. Addition of 10(-6) mol/l ACh to the perfusate increased glucose-stimulated insulin secretion. Also, 10(-6) mol/l ACh, 10(-7) mol/l norepinephrine, as well as a combination of both, induced marked glucagon secretion, this was suppressed by high blood glucose level. Although simultaneous addition of 10(-6) mol/l ACh and 10(-7) mol/l norepinephrine induced only a slight increase in glucagon secretion in response to glucopenia, there was a significant increase in glucagon secretion in conjunction with an ambient decrease in insulin. Histopathological examination revealed a marked decline in acetylcholinesterase and monoamine-oxidase activities in the islets of streptozotocin-induced diabetic rats. We speculate that reduction of the potentiating effects of ACh and norepinephrine lessens glucose sensitivity of islet beta and alpha cells in this rat model of diabetes.
为阐明链脲佐菌素诱导的糖尿病大鼠胰岛激素分泌对葡萄糖不敏感的机制,我们使用胰腺灌注标本,研究了乙酰胆碱(ACh)和去甲肾上腺素对胰岛素和胰高血糖素分泌的影响,这些分泌是对葡萄糖浓度变化的反应。链脲佐菌素诱导的糖尿病大鼠在血糖水平为5.6 mmol/l时的基础胰岛素分泌显著高于对照组,基础胰高血糖素分泌显著低于对照组,高血糖(16.7 mmol/l)和低血糖(1.4 mmol/l)浓度均不影响胰岛素或胰高血糖素分泌。向灌注液中添加10(-6) mol/l ACh可增加葡萄糖刺激的胰岛素分泌。此外,10(-6) mol/l ACh、10(-7) mol/l去甲肾上腺素以及两者的组合均可诱导显著的胰高血糖素分泌,高血糖水平可抑制这种分泌。尽管同时添加10(-6) mol/l ACh和10(-7) mol/l去甲肾上腺素仅在低血糖时诱导胰高血糖素分泌略有增加,但随着胰岛素的环境性降低,胰高血糖素分泌有显著增加。组织病理学检查显示,链脲佐菌素诱导的糖尿病大鼠胰岛中的乙酰胆碱酯酶和单胺氧化酶活性显著下降。我们推测,在这种糖尿病大鼠模型中,ACh和去甲肾上腺素的增强作用减弱会降低胰岛β细胞和α细胞对葡萄糖的敏感性。