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: 6116722
• 负责人: PETER J HAVEL
• 金额: $ 4.41万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116722
• 关键词: Mammalia; carbohydrates; diabetes mellitus; endocrine gland /system; hormones; nervous system; nutrition; nutrition related tag

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.

显著性低血糖是临床上的主要问题， 胰岛素治疗的糖尿病 低血糖症限制了病人 维持适当的血糖水平控制， 预防糖尿病的毁灭性并发症。 胰高血糖素升高 胰高血糖素分泌是抵抗低血糖的主要防御，但胰高血糖素 在糖尿病中对低血糖的反应受损。 的病因 这种损伤的理解很少，但可能涉及到 自主神经系统（ANS）刺激胰高血糖素分泌， ANS对几个物种的这种反应有贡献。 但 ANS在人类中的作用一直存在争议。 目的 研究ANS在低血糖诱导的胰高血糖素中的重要性 分泌和ANS缺陷在受损反应中的作用， 糖尿病的灵长类动物模型 结果我们调查了ANS 使用两种方法对低血糖诱导的胰高血糖素分泌的贡献 药理学方法（阻断神经节神经传递 与三甲氧苯甲烷或ANS受体阻滞剂），以损害ANS输入 对胰腺的影响。 我们发现， 在介导胰高血糖素反应中起主要作用， 低血糖2.0 mmol/L。 根据这些结果，我们进行了 一项针对人类的研究发现， 低血糖诱导的胰高血糖素分泌。 非人 灵长类动物研究提供了重要的背景和方法 人类研究的信息。 未来的方向我们现在 检查胰高血糖素分泌的自主调节， 实验性糖尿病猴低血糖及其损害 链脲佐菌素给药诱导的模型，以研究 干预措施，可以防止低血糖诱导的损害 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 DK 50129出版物Taborsky， Gerald J，Ahren，Bo，and Peter J. Havel. 自治调解 低血糖时胰高血糖素的分泌对受损 1型糖尿病的A细胞反应，糖尿病的前景，糖尿病 47 995-1005，1998年。