The effect of experimental insulin deficiency on glucagon secretion
Open Access
- 1 September 1971
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 50 (9), 1992-1999
- https://doi.org/10.1172/jci106691
Abstract
Suppression of pancreatic glucagon secretion by hyperglycemia is a characteristic of normal alpha cell function. However, in diabetic subjects, plasma glucagon is normal or high despite hyperglycemia. It seemed possible that the presence of glucose or its metabolites within the alpha cell might be essential for suppression of glucagon secretion, and that in diabetes an intracellular deficiency of glucose secondary to insulin lack might be responsible for the nonsuppressibility. The present study was designed to determine the effect upon glucagon secretion of blockade of glucose metabolism and of experimental insulin deficiency. Blockade of glucose metabolism was induced in dogs by administration of 2-deoxyglucose or mannoheptulose. A striking rise in glucagon was observed despite accompanying hyperglycemia and hyperinsulinemia, which, in the case of mannoheptulose, was induced by infusing crystalline insulin. To determine if insulin lack also causes paradoxical hyperglucagonemia, dogs were made severely diabetic by alloxan. Fasting glucagon levels ranged from 3 to 22 times normal despite severe hyperglycemia, and were quickly restored to normal by infusing insulin. Diabetes induced in rats by anti-insulin serum was also associated with significant elevation in plasma glucagon. However, diazoxide-induced insulin lack did not increase glucagon in dogs. It is concluded that normal suppression of glucagon secretion by hyperglycemia does not occur when glucose metabolism is blocked or when severe insulin deficiency is produced. It is suggested that normal glucose metabolism within the alpha cell may be an insulin-requiring process without which hyperglycemic suppression of glucagon release cannot occur.Keywords
This publication has 17 references indexed in Scilit:
- [Evolution of hormonal parameters (glucagon, cortisol, growth hormone) and energetic parameters (glucose, fatty acids, free glycerol) in 10 severe cases of diabetic acido-ketosis under treatment].1969
- Hyperglycemia and Inhibition of Insulin Secretion during Administration of Diazoxide and Trichlormethiazide in ManDiabetes, 1969
- Control of Pancreatic Glucagon Secretion by GlucoseDiabetes, 1969
- [Inhibitors of insulin secretion].1968
- Characterization of response of circulating glucagon to intraduodenal and intravenous administration of amino acidsJCI Insight, 1968
- Effect of Epinephrine on Insulin Release in Man induced by SecretinNature, 1967
- The Effects of Secretin, Pancreozymin, and Gastrin on Insulin and Glucagon Secretion in Anesthetized Dogs *JCI Insight, 1967
- Immunoreactive insulin, suppressible, and non suppressible insulinlike activities in rats after administration of glucose and induction of hyperglycaemia by mannoheptuloseDiabetologia, 1966
- Coated Charcoal Immunoassay of InsulinJournal of Clinical Endocrinology & Metabolism, 1965
- Inhibition of glucose phosphorylation by mannoheptuloseBiochemical Journal, 1964