EPINEPHRINE-INDUCED INSULIN RESISTANCE IN MAN
EPINEPHRINE-INDUCED INSULIN RESISTANCE IN MAN
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DOI：
10.1172/jci109718
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发表时间：
1980-01-01
影响因子：
15.9
通讯作者：
DEFRONZO, RA
中科院分区：
文献类型：
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作者：
DEIBERT, DC;DEFRONZO, RA
应激后内源性肾上腺素 (E) 释放以及外源性 E 输注会导致糖耐量受损。先前对人和动物的研究表明，E 的这种作用显然是由于抑制胰岛素 [I] 分泌和增加肝葡萄糖产生而引起的。然而，E 对组织对 I 敏感性的影响，以及外周与肝脏抵抗对 I 作用受损的相对贡献，尚未确定。使用 I 夹技术对九名年轻的正常体重受试者进行了研究。 Plasma I 由 .apprx 筹集。 100μU[单位]ml，同时通过可变葡萄糖输注将血浆葡萄糖浓度维持在基础水平。在这些血糖正常的条件下，代谢的葡萄糖量等于葡萄糖输注速率，并且是组织对 I 敏感性的量度。受试者接受了 4 项研究：I（每分钟 42.6 mU/m2）、I 加 E（每分钟 0.05 μg/kg）、I 加 E 加普萘洛尔（每分钟 1.43 μg/kg）和 I 加普萘洛尔。在单独给药期间，葡萄糖代谢平均为5.49±。每分钟 0.58 毫克/公斤。当 E 与 I 一起输注时，葡萄糖代谢下降 41%，降至每分钟 3.26 mg/kg (P < 0.001)。单独使用 I 后，肝葡萄糖产量下降 92% 至 0.16 .+-。每分钟 0.08 毫克/公斤。尽管血浆I水平>100μU/ml，但E的添加与葡萄糖产生的延迟和不完全抑制相关(P<0.01)。当普萘洛尔与 E 一起给药时，总葡萄糖代谢恢复至对照值，并且肝葡萄糖产生正常抑制。单独的普萘洛尔对 I 介导的葡萄糖代谢没有影响。显然，E主要通过β-肾上腺素能受体发挥作用，显着损害组织对血浆I水平增加的敏感性；这种作用是由外周和肝脏对 I 作用的抵抗引起的。
Endogenous epinephrine (E) release after stress as well as exogenous E infusion result in impaired glucose tolerance. Previous studies of man and animals have demonstrated that this effect of E apparently results from inhibition of insulin [I] secretion and augmentation of hepatic glucose production. However, the effect of E on tissue sensitivity to I, and the relative contributions of peripheral vs. hepatic resistance to impaired I action, were not defined. Nine young normal-weight subjects were studied with the I clamp technique. Plasma I was raised by .apprx. 100 .mu.U[unit]ml while plasma glucose concentration was maintained at basal levels by a variable glucose infusion. Under these conditions of euglycemia, the amount of glucose metabolized equals the glucose infusion rate and is a measure of tissue sensitivity to I. Subjects received 4 studies: I (42.6 mU/m2 per min), I plus E (0.05 .mu.g/kg per min), I plus E plus propranolol (1.43 .mu.g/kg per min), and I plus propranolol. During I administration alone, glucose metabolism averaged 5.49 .+-. 0.58 mg/kg per min. When E was infused with I, glucose metabolism fell by 41% to 3.26 mg/kg per min (P < 0.001). After I alone, hepatic glucose production declined by 92% to 0.16 .+-. 0.08 mg/kg per min. E addition was associated with a delayed and incomplete suppression of glucose production (P < 0.01) despite plasma I levels > 100 .mu.U/ml. When propranolol was administered with E, total glucose metabolism was restored to control values and hepatic glucose production suppressed normally. Propranolol alone had no effect on I-mediated glucose metabolism. Apparently E, acting primarily through a .beta.-adrenergic receptor, markedly impairs tissue sensitivity to an increase in plasma I levels; this effect results from both peripheral and hepatic resistance to the action of I.