AUTONOMIC NERVOUS SYSTEM REGULATION OF GLUCAGON SECRETION IN RHESUS MONKEYS

显著性低血糖是临床上的主要问题， 胰岛素治疗的糖尿病 胰高血糖素分泌增加是 对低血糖的防御，但胰高血糖素对低血糖的反应 在糖尿病中受损。 这种损伤的病因学很差， 可以理解，但可能涉及自主神经系统的故障 (ANS)刺激胰高血糖素分泌，因为ANS有助于 这种反应在几个物种。 然而，ANS在 人类是有争议的。 目的了解 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受损反应中的作用 糖尿病 结果我们调查了ANS对 使用两种药理学方法抑制低血糖诱导的胰高血糖素分泌 方法（用曲美沙芬阻断神经节神经传递 或ANS受体阻滞剂），以损害ANS输入胰腺， 清醒的恒河猴。 我们发现ANS在 介导2.0 mmol/L低血糖期间的胰高血糖素反应。 这些结果在第31届年度会议上公布， 欧洲糖尿病协会和手稿现已出版。 基于这些结果，我们在人类受试者中进行了一项研究 并发现了类似的自主神经对低血糖诱导的 人体胰高血糖素分泌。 包含这些结果的手稿 已经出版了。 非人类灵长类动物的研究提供了至关重要的 人类研究的背景和方法学信息。 在 此外，这些结果导致了一篇关于 ANS调节胰高血糖素治疗1型糖尿病的意义 糖尿病 这些实验一起帮助我们 私人研究所获得国家卫生研究院的拨款，从1997年4月开始。 未来 我们现在开始进行新的实验， 低血糖时胰高血糖素的自主调节及其意义 实验性糖尿病猴子的损伤。 关键词 低血糖，胰高血糖素，自主神经系统，糖尿病

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