The effect of experimental insulin deficiency on glucagon secretion
TLDR
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, and it is suggested that normal glucose metabolism within the alpha cell may be an insulin-requiring process without which hyperglycemic suppressed glucagon release cannot occur.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.read more
Citations
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Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect.
TL;DR: Despite excessive glucagon responses to infusion of arginine, plasma glucagon did not rise in six juvenile-type diabetics during severe insulin-induced hypoglycemia, whereas glucagon in the controls rose significantly, indicating that pancreatic alpha cells are insensitive to glucose even in the presence of large amounts of circulating insulin.
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Interplay of nutrients and hormones in the regulation of insulin release.
TL;DR: The concept that the potent in vivo insulin-releasing action of glucose and leucine is not only dependent on their fuel capacity in pancreatic B cells but also on the concurrent cAMP levels is strongly supported.
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Leptin and the Central Nervous System Control of Glucose Metabolism
TL;DR: This review highlights growing evidence that leptin action in the central nervous system plays a key role in both body fat stores and blood glucose levels and raises interesting new possibilities for the treatment of diabetes and related disorders.
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Insulin within islets is a physiologic glucagon release inhibitor.
TL;DR: It is concluded that insulin maintains an ongoing restraint upon alpha cell secretion and in its absence causes hectic hypersecretion of glucagon, which probably occurs largely in the intravascular compartment.
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Intra-islet insulin suppresses glucagon release via GABA-GABAA receptor system
Elaine Xu,Elaine Xu,Mohan Kumar,Mohan Kumar,Yi Zhang,Yi Zhang,William Ju,William Ju,Toshiyuki Obata,Nina Zhang,Shiying Liu,Anna Wendt,Shaoping Deng,Yousuke Ebina,Michael B. Wheeler,Matthias Braun,Matthias Braun,Qinghua Wang,Qinghua Wang +18 more
TL;DR: Insulin induces activation of GABAA receptors in the alpha cells by receptor translocation via an Akt kinase-dependent pathway that leads to membrane hyperpolarization in thealpha cells and, ultimately, suppression of glucagon secretion, and it is proposed that defects in this pathway contribute to diabetic hyperglycemia.
References
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Studies of pancreatic alpha cell function in normal and diabetic subjects
TL;DR: The findings suggest that alpha cell function is inappropriately increased in diabetes mellitus and could play a significant role in the diabetic syndrome.