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。低血糖限制了患者的能力 要保持足够的血糖控制水平，以便 预防糖尿病的破坏性并发症。胰高血糖素升高 分泌是抵抗低血糖的主要防御措施，但胰高血糖素 糖尿病患者对低血糖的反应受损。该病的病因学 人们对这种损害知之甚少，但可能涉及 自主神经系统(ANS)刺激胰升糖素分泌 有几个物种的ANS参与了这一反应。然而， ANS在人类中的作用一直存在争议。目标为 探讨ANS在低血糖诱导的胰升糖素中的作用 分泌物和ANS缺陷在老年痴呆反应受损中的作用 糖尿病的灵长类模型。结果我们调查了ANS 两种药物在低血糖诱导的胰升糖素分泌中的作用 药理学方法(阻断神经节神经传递 使用曲美沙潘或ANS受体阻滞剂)以损害ANS输入 有意识的恒河猴的胰腺。我们发现ANS 在调节胰高血糖素反应中起着重要作用 根据这些结果，我们进行了 一项对人类受试者的研究发现了类似的自主神经贡献 人类低血糖诱导的胰升糖素分泌。非人类 灵长类动物研究提供了重要的背景和方法 为人体研究提供信息。我们现在所处的未来方向 检测胰升糖素分泌的自主神经调节 实验性糖尿病猴的低血糖及其损害 以链脲佐菌素诱导的动物模型为研究对象 可预防低血糖所致损害的干预措施 胰高血糖素分泌。关键词低血糖、胰高血糖素、自主神经 神经系统，糖尿病基金，NIH DK50129出版物，塔博斯基， 杰拉尔德·J、阿伦、波和彼得·J·哈维尔。自主调解 低血糖时高血糖素分泌对受损患者的影响 1型糖尿病中的A细胞反应，糖尿病，糖尿病的前景 47995-1005,1998。

Significance Hypoglycemia is major clinical problem in insulin-treated diabetes. Hypoglycemia limits the ability of patients to maintain adequate control blood of glucose levels in order to prevent the devastating complications of 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 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. 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. The nonhuman primate studies provided crucial background and methodological information for the human studies. Future Directions We are now examining the autonomic regulation glucagon secretion during hypoglycemia and its impairment in monkeys with experimental diabetes induced by streptozotocin administration as a model to investigate interventions that may prevent the impairment of hypoglycemia-induced glucagon secretion. KEY WORDS hypoglycemia, glucagon, autonomic nervous system, diabetes FUNDING NIH DK50129 PUBLICATIONS Taborsky, Gerald J, Ahren, Bo, and Peter J. Havel. Autonomic Mediation of Glucagon Secretion During Hypoglycemia Implications for Impaired A-Cell Responses in Type-1 Diabetes, Perspective in Diabetes, Diabetes 47 995-1005, 1998.