The Lilly Lecture 1976: Insulin, Glucagon, and Somatostatin in Normal Physiology and Diabetes Mellitus
The Lilly Lecture 1976: Insulin, Glucagon, and Somatostatin in Normal Physiology and Diabetes Mellitus
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1976 年礼来讲座：正常生理和糖尿病中的胰岛素、胰高血糖素和生长抑素
作者：
P. Felig;J. Wahren;R. Sherwin;R. Hendler
本文综述了胰岛素和胰高血糖素在正常生理和糖尿病中的作用。在正常人中，葡萄糖摄入伴随着胰岛素的升高和胰高血糖素的下降，并主要在肝脏中处理，因为肝脏对这两种激素都很敏感。然而，注射生理量的胰高血糖素表明，胰岛素分泌而不是胰高血糖素抑制是决定葡萄糖处置的主要因素。此外，血糖的轻微升高会引起胰岛素浓度的增加，并在血浆胰高血糖素没有变化的情况下抑制肝脏葡萄糖输出。胰高血糖素的主要生理作用是防止伴随非碳水化合物（蛋白质）介导的胰岛素分泌而产生的低血糖。在糖尿病患者和正常患者中，胰高血糖素对肝脏葡萄糖生成的刺激作用是短暂的。胰高血糖素的升高或I/G比值的变化，只有在存在绝对胰岛素缺乏或胰高血糖素产生药理学上的升高时，才会导致葡萄糖耐量或糖尿病控制的恶化。在给予生长抑素后，观察到正常受试者长时间的低胰岛素血症导致空腹高血糖，而基础胰高血糖素分泌不足。在糖尿病患者中，生长抑素产生的餐后高血糖的改善可以通过其抑制胃肠道碳水化合物吸收的作用来解释。结论：胰岛素缺乏是糖尿病的主要病理生理障碍。虽然高血糖素可能会加重胰岛素缺乏的后果，但它对糖尿病的发展既不是充分的，也不是必要的。
Studies are reviewed in which the roles of insulin and glucagon in normal physiology and in diabetes are examined. In normal man, glucose ingestion is accompanied by a rise in insulin and fall in glucagon and is primarily disposed of in the liver, an organ sensitive to both hormones. However, infusions of glucagon in physiologic amounts indicate that insulin secretion rather than glucagon inhibition is the primary factor determining glucose disposal. Furthermore, minor elevations in blood glucose elicit increments in insulin concentration and inhibition of hepatic glucose output in the absence of changes in plasma glucagon. The primary physiologic role of glucagon is to prevent the hypoglycemia that would otherwise accompany noncarbohydrate (protein)-mediated insulin secretion. In diabetic as well as normal patients the stimulatory effect of glucagon on hepatic glucose production is evanescent. Increases in glucagon or changes in the I/G ratio can bring about deterioration in glucose tolerance or in diabetic control only so long as absolute insulin deficiency is present or pharmacologic elevations in glucagon are produced. After somatostatin administration, prolonged hypoinsulinemia in normal subjects is observed to result in fasting hyperglycemia in the absence of basal glucagon secretion. In diabetic patients the improvement in postprandial hyperglycemia produced by somatostatin can be accounted for by its inhibitory action on carbohydrate absorption in the gastrointestinal tract. It is concluded that insulin deficiency is the primary pathophysiologic disturbance in diabetes. While glocagon may worsen the consequences of insulin lack, it is neither sufficient nor necessary for the development of diabetes.