AUTONOMIC NERVOUS SYSTEM REGULATION OF GLUCAGON SECRETION IN RHESUS MONKEYS

恒河猴胰高血糖素分泌的自主神经系统调节

• 批准号: 6277965
• 负责人: PETER J HAVEL
• 金额: $ 5.21万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277965
• 关键词: Mammalia; Primates; carbohydrates; diabetes mellitus; endocrine gland /system; hormones; nervous system; nutrition; nutrition related tag

Significance Hypoglycemia is major clinical problem in insulin-treated diabetes. Increased glucagon secretion is a primary defense against hypoglycemia, but glucagon responses to hypoglycemia are impaired in diabetes. The etiology of the impairment is poorly understood, but may involve a failure of the autonomic nervous system (ANS) to stimulate glucagon secretion since the ANS contributes to this response in several species. However, the role of the ANS in humans has been controversial. Objectives To investigate the importance of the ANS in hypoglycemia-induced glucagon secretion and the role of ANS deficits in impaired responses in a primate model of diabetes. Results We investigated the ANS contribution to hypoglycemia-induced glucagon secretion using two pharmacological approaches (blockade of ganglionic neurotransmission with trimethaphan or ANS receptor blockade) to impair the ANS inputs to the pancreas in conscious rhesus macaques. We found that the ANS has a major role in mediating the glucagon response during hypoglycemia of 2.0 mmol/L. These results were presented at the 31st Annual Meeting of the European Diabetes Association and a manuscript has now been published. Based on these results, we have conducted a study in human subjects and found a similar autonomic contribution to hypoglycemia-induced glucagon secretion in humans. A manuscript containing these results has been published. The nonhuman primate studies provided crucial background and methodological information for the human studies. In addition these results led to the writing of a review article on the implications of ANS regulation of glucagon for treatment of type-1 diabetes. Together these experiments were instrumental in allowing the P.I to obtain an NIH grant which began in April, 1997. Future Directions We are now starting new experiments to examine the autonomic regulation glucagon secretion during hypoglycemia and its impairment in monkeys with experimental diabetes. KEYWORDS hypoglycemia, glucagon, autonomic nervous system, diabetes

意义 低血糖是主要的临床问题 胰岛素治疗的糖尿病。 胰高血糖素分泌增加是首要原因 对低血糖的防御，但胰高血糖素对低血糖的反应 因糖尿病而受损。 损伤的病因尚不明确 理解，但可能涉及自主神经系统故障 (ANS) 刺激胰高血糖素分泌，因为 ANS 有助于 几个物种都有这种反应。 然而，ANS 在 人类一直存在争议。 目标 调查 ANS 在低血糖诱导的胰高血糖素分泌中的重要性 ANS 缺陷在灵长类动物模型反应受损中的作用 糖尿病。 结果 我们调查了 ANS 对 使用两种药理学方法诱导低血糖诱导胰高血糖素分泌 方法（用三甲芬阻断神经节神经传递 或 ANS 受体阻断）以损害胰腺的 ANS 输入 有意识的恒河猴。 我们发现 ANS 在以下方面发挥着重要作用： 在 2.0 mmol/L 低血糖期间介导胰高血糖素反应。 这些成果已在第 31 届年会上公布 欧洲糖尿病协会的一份手稿现已出版。 根据这些结果，我们对人类受试者进行了一项研究 并发现了类似的自主神经对低血糖的贡献 人体胰高血糖素的分泌。 包含这些结果的手稿 已发布。 非人类灵长类动物研究提供了至关重要的 人类研究的背景和方法信息。 在 此外，这些结果导致了一篇评论文章的撰写 ANS 调节胰高血糖素对治疗 1 型糖尿病的影响 糖尿病。 这些实验共同有助于实现 P.I 获得 NIH 资助，该资助于 1997 年 4 月开始。 未来 方向 我们现在开始新的实验来检查 低血糖时自主神经调节胰高血糖素分泌及其影响 患有实验性糖尿病的猴子的损伤。 关键词 低血糖，胰高血糖素，自主神经系统，糖尿病