AUTONOMIC NERVOUS SYSTEM REGULATION OF GLUCAGON SECRETION IN RHESUS MONKEYS

意义低血糖是糖尿病的主要临床问题 胰岛素治疗的糖尿病。胰升糖素分泌增加是主要的 预防低血糖，但胰升糖素对低血糖的反应 都会因糖尿病而受损。损伤的病因很差。 可以理解，但可能涉及到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中都存在。然而，ANS在这方面的作用 人类一直备受争议。目的：调查 ANS在低血糖诱导的胰高血糖素分泌中的重要性 在灵长类动物模型中ANS缺陷在反应受损中的作用 糖尿病。结果我们调查了ANS对 两种药物诱导低血糖诱导的胰升糖素分泌 入路(用曲美沙芬阻断神经节细胞神经传递 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在体内起着重要的作用 介导2.0 mmol/L低血糖时的胰升糖素反应 这些成果已在第31届世界银行年会上公布。 欧洲糖尿病协会和一份手稿现已出版。 基于这些结果，我们在人类受试者身上进行了一项研究 并发现了类似的自主神经对低血糖的作用 人类的胰升糖素分泌。包含这些结果的手稿 已经出版了。非人灵长类动物的研究提供了至关重要的 人体研究的背景和方法信息。在……里面 此外，这些结果导致了一篇关于 ANS对胰升糖素的调节在1型糖尿病治疗中的意义 糖尿病。这些实验加在一起有助于 从1997年4月开始，P.I获得了NIH的拨款。未来 我们现在正在开始新的实验来研究 低血糖时胰高血糖素分泌的自主调节及其机制 实验性糖尿病猴子的损害。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