Role of epinephrine-mediated beta-adrenergic mechanisms in hypoglycemic glucose counterregulation and posthypoglycemic hyperglycemia in insulin-dependent diabetes mellitus.
Role of epinephrine-mediated beta-adrenergic mechanisms in hypoglycemic glucose counterregulation and posthypoglycemic hyperglycemia in insulin-dependent diabetes mellitus.
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DOI：
10.1172/jci110455
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发表时间：
1982-02
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影响因子：
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通讯作者：
Dennis A. Popp;Suresh D. Shah;P. Cryer
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文献类型：
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作者：
Dennis A. Popp;Suresh D. Shah;P. Cryer
与非糖尿病对照组相比，胰岛素依赖型糖尿病患者在快速静脉注射0.075 U/kg普通胰岛素后，表现出与非糖尿病对照组相似但有一定延迟的血糖最低点、低血糖恢复延迟和低血糖后高血糖。这些异常与糖尿病患者的胰升糖素分泌反应显著降低、肾上腺素分泌反应部分降低以及注射的胰岛素清除延迟有关，并可能与此有关。由于胰升糖素通常在低血糖时起主要作用，而肾上腺素分泌的增加在很大程度上弥补了胰升糖素的缺乏，我们推测，与非糖尿病患者相比，对低血糖表现出较弱的胰升糖素分泌反应的IDDM患者将更依赖肾上腺素来促进低血糖中的血糖恢复。为了验证这一假说，在非糖尿病对照组和IDDM患者中，比较了心得安阻断β-肾上腺素能阻滞剂和生理盐水输注期间的血糖抵消调节。对照组的血糖反调节不受β-肾上腺素能受体阻滞剂的影响。相比之下，糖尿病患者在使用β-肾上腺素能受体阻滞剂时，从低血糖中恢复血糖的能力明显受损。这一发现证实了这类患者更多地依赖肾上腺素介导的β-肾上腺素能机制来促进低血糖患者血糖恢复的假设，并表明所测量的胰高血糖素分泌缺陷在IDDM患者中具有重要的功能。此外，在这些研究的时间框架内，这些患者的降糖后高血糖可通过β-肾上腺素能受体阻滞剂来预防。在糖尿病患者中，就β-肾上腺素能受体阻滞剂限制血糖升高的程度而言，存在相当大的异质性。我们的结论是：(A)IDDM患者在不同程度上依赖肾上腺素介导的β-肾上腺素能机制来促进低血糖患者的血糖恢复，这种依赖程度与个体患者因低血糖而分泌高血糖素的剩余能力成反比；(B)交感神经肾上腺激活，加上无法分泌胰岛素，在IDDM患者发生低血糖后高血糖的发病机制中起着重要作用。
Initially euglycemic (overnight insulin-infused) patients with insulin-dependent diabetes mellitus (IDDM), compared with nondiabetic controls, exhibit similar, but somewhat delayed plasma glucose nadirs, delayed glucose recovery from hypoglycemia, and posthypoglycemic hyperglycemia after the rapid intravenous injection of 0.075 U/kg of regular insulin. These abnormalities are associated with and potentially attributable to markedly diminished glucagon secretory responses, partially reduced epinephrine secretory responses and delayed clearance of injected insulin in the diabetic patients. Because glucagon normally plays a primary role in hypoglycemic glucose counterregulation and enhanced epinephrine secretion largely compensates for glucagon deficiency, we hypothesized that patients with IDDM, who exhibit diminished glucagon secretory responses to hypoglycemia, would be more dependent upon epinephrine to promote glucose recovery from hypoglycemia than are nondiabetic persons. To test this hypothesis, glucose counterregulation during beta-adrenergic blockade with propranolol was compared with that during saline infusion in both nondiabetic controls and in patients with IDDM. Glucose counterregulation was unaffected by beta-adrenergic blockade in controls. In contrast, glucose recovery from hypoglycemia was significantly impaired during beta-adrenergic blockade in diabetic patients. This finding confirms the hypothesis that such patients are more dependent upon epinephrine-mediated beta-adrenergic mechanisms to promote glucose recovery from hypoglycemia and indicates that the measured deficiency of glucagon secretion is functionally important in patients with IDDM. Further, in the time frame of these studies, posthypoglycemic hyperglycemia was prevented by beta-adrenergic blockade in these patients. There was considerable heterogeneity among the diabetic patients with respect to the degree to which beta-adrenergic blockade limited the posthypoglycemic rise in plasma glucose. This rise was directly related to the degree of residual glucagon secretion and inversely related to plasma-free insulin concentrations.THUS, WE CONCLUDE: (a) that patients with IDDM are, to varying degrees, dependent upon epinephrine-mediated beta-adrenergic mechanisms to promote glucose recovery from hypoglycemia and that the degree of this dependence upon epinephrine is an inverse function of the residual capacity to secrete glucagon in response to hypoglycemia in individual patients; (b) that sympathoadrenal activation, coupled with the inability to secrete insulin, plays an important role in the pathogenesis of posthypoglycemic hyperglycemia in patients with IDDM.