Autonomic mediation of glucagon secretion during insulin-induced hypoglycemia in rhesus monkeys
Autonomic mediation of glucagon secretion during insulin-induced hypoglycemia in rhesus monkeys
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DOI：
10.2337/diabetes.45.7.960
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发表时间：
1996-07-01
期刊：
影响因子：
7.7
通讯作者：
Valverde, C
中科院分区：
文献类型：
--
作者：
Havel, PJ;Valverde, C
在包括犬、小鼠和大鼠在内的几种动物中，自主神经激活介导了胰岛素诱导的低血糖期间胰高血糖素分泌的大部分增加。然而，自主神经系统在人类低血糖期间增加胰高血糖素的作用仍然存在争议，并且以前没有在非人灵长类动物中进行过研究。通过两种独立的药理学方法研究了非人灵长类动物在低血糖期间对胰高血糖素分泌的自主贡献。胰高血糖素反应钳夹胰岛素诱导的低血糖症进行了比较清醒的恒河猴在存在或不存在的神经节阻滞与曲美沙芬，或在联合毒蕈碱和肾上腺素能受体阻滞与阿托品，普萘洛尔，妥拉苏林。胰岛素诱发的低血糖（血糖= 1.9 +/- 0.1 mmol/l）激活胰腺的副交感神经，通过血浆胰腺多肽（PP）水平升高进行评估（Delta = 135.0 +/- 36.8 pmol/l，P < 0.01），通过血浆肾上腺素（EPI）升高评估产生交感肾上腺激活（Delta = 22.3 +/- 2.95 nmol/l，P < 0.0005）和去甲肾上腺素（NE）（Delta = 3.72 +/- 0.77 nmol/l，P < 0.0025）和血浆免疫反应性胰高血糖素（IRG）增加（Delta = 920 +/- 294 ng/l，P < 0.025）。用曲美沙芬阻断烟碱神经节可防止副交感神经（Δ PP = 16.5 +/- 16.3 pmol/l，与对照组相比P < 0.01）和交感肾上腺（Δ EPI = 1.52 +/- 0.98 nmol/l; Δ NE = -0.62 +/- 0.24 nmol/l，均P < 0.0025，与对照组相比），并抑制IRG反应70%（Delta = 278 +/- 67 ng/l，与对照组相比P < 0.025）。毒蕈碱受体和肾上腺素能受体联合阻断可减少副交感神经激活（Δ PP = 48.3 +/- 16.3 pmol/l，P < 0.01，与对照组相比），并以与神经节阻断相似的程度抑制IRG反应（Δ IRG = 284 +/- 60 ng/l，与对照组相比P < 0.025）。这些结果通过两种独立的药理学方法证明，在一种非人灵长类动物中，自主激活对2.0 mmol/l低血糖期间胰高血糖素分泌增加有实质性贡献。
Autonomic activation mediates the majority of the increase of glucagon secretion during insulin-induced hypoglycemia in several species including dogs, mice, and rats. However, the role of the autonomic nervous system to increase glucagon during hypoglycemia in humans remains controversial, and investigations in nonhuman primates have not been previously conducted. The autonomic contribution to glucagon secretion during hypoglycemia in a nonhuman primate was examined by two independent pharmacological approaches. Glucagon responses to clamped insulin-induced hypoglycemia were compared in conscious rhesus monkeys in the presence or absence of ganglionic blockade with trimethaphan, or during combined muscarinic and adrenergic receptor blockade with atropine, propranolol, and tolazoline. Insulin-induced hypoglycemia (plasma glucose = 1.9 +/- 0.1 mmol/l) activated parasympathetic nerves to the pancreas as assessed by increased plasma pancreatic polypeptide (PP) levels (Delta = 135.0 +/- 36.8 pmol/l, P < 0.01), produced sympathoadrenal activation as assessed by elevations of plasma epinephrine (EPI) (Delta = 22.3 +/- 2.95 nmol/l, P < 0.0005) and norepinephrine (NE) (Delta = 3.72 +/- 0.77 nmol/l, P < 0.0025) and increased plasma immunoreactive glucagon (IRG) (Delta = 920 +/- 294 ng/l, P < 0.025). Nicotinic ganglionic blockade with trimethaphan prevented parasympathetic (Delta PP = 16.5 +/- 16.3 pmol/l, P < 0.01 vs. control) and sympathoadrenal (Delta EPI = 1.52 +/- 0.98 nmol/l; Delta NE = -0.62 +/- 0.24 nmol/l, both P < 0.0025 vs. control) activation during hypoglycemia and inhibited the IRG response by 70% (Delta = 278 +/- 67 ng/l, P < 0.025 vs. control). Combined muscarinic and adrenergic receptor blockade reduced parasympathetic activation (Delta PP = 48.3 +/- 16.3 pmol/l, P < 0.01 vs. control) and inhibited the IRG response by a similar degree to ganglionic blockade (Delta IRG = 284 +/- 60 ng/l, P < 0.025 vs. control). These results demonstrate by two independent pharmacological approaches that autonomic activation makes a substantial contribution to increased glucagon secretion during hypoglycemia of similar to 2.0 mmol/l in a species of nonhuman primate.