Abnormal alpha cell function in diabetics response to insulin.

Roger H Unger, L. L. Madison, W. A. Muller

Research output: Chapter in Book/Report/Conference proceedingChapter

63 Scopus citations

Abstract

The extremely high levels of glucagon recently observed in dogs with severe alloxan-induced diabetes decline promptly and precipitously to normal as soon as exogenous insulin is infused. This suggests that the normal response of the pancreatic alpha cell to hyperglycemia requires the presence of circulating insulin. To determine if the relative hyperglucagonemia of human diabetics responds similarly to insulin repletion, the plasma glucagon response of ten adult-type diabetic patients to a large, predominantly carbohydrate meal was determined with and without the simultaneous forty-five-minute intravenous infusion of glucagon free insulin (0.12 to 0.2 U./kg.). The glucagon response to the carbohydrate meal during prompt and super normal hyperinsulinemia resulting from the infusion did not differ from that of the control meal, i.e. normal suppression of glucagon by hyperglycemia was not restored by the abundance of circulating insulin.To determine if still higher plasma levels of insulin would overcome the hyposuppressibility of the diabetic alpha cell to hyperglycemia, 0.6 U. per kilogram per hour of insulin was infused at a constant rate for two hours together with 0.6 gm. per kilogram per hour of glucose to prevent hypoglycemia.Insulin levels of more than 1,200 μU. per milliliter were thus attained. Under these conditions, plasma glucagon declined from a mean preinfusion level of 97 pg./ml. (SEM ± 11) to a nadir of 75 pg./ml. (SEM ± 10) ninety minutes later. This slow, modest, statistically significant (p < 0.01)decline differed strikingly from the response of eight non diabetic patients given intravenous glucose alone; in these subjects, at a comparable level of hyperglycemia, glucagon declined from a mean fasting level of 90 pg./ml. (SEM ± 8) to 57 pg./ml. (SEM ± 8) within thirty minutes, despite an insulin rise to only 46 μU./ml.It was concluded that in human diabetics the acute restoration of plasma insulin, even to supernormal levels, does not promptly restore to normal the alpha cell responsiveness to hyperglycemia. Simple insulin lack may not, therefore,adequately explain the alpha cell abnormality in human diabetes.

Original languageEnglish (US)
Title of host publicationDiabetes
Pages301-307
Number of pages7
Volume21
Edition5
StatePublished - 1972

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Unger, R. H., Madison, L. L., & Muller, W. A. (1972). Abnormal alpha cell function in diabetics response to insulin. In Diabetes (5 ed., Vol. 21, pp. 301-307)