The effect of experimental insulin deficiency on glucagon secretion
Open accessAbstract
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.
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Hyperglucagonemia contributes to hyperglycemia in uDM, at least in part by driving hepatic expression of gluconeogenic genes G6Pase and Pepck.
“Several lines of evidence suggest that hyperglucagonemia contributes to the hyperglycemia in uDM, at least in part by driving the hepatic expression of the gluconeogenic genes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate kinase (Pepck) (47, 123).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [123]
Elevated plasma glucagon and corticosterone levels are implicated in the pathogenesis of hyperglycemia in uDM.
“Elevated plasma glucagon and corticosterone levels are implicated in the pathogenesis of hyperglycemia in uDM (29 -31).”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [29]
Hyperglucagonemia contributes to diabetic hyperglycemia in part by driving hepatic expression of Pepck and G6Pase.
“Hyperglucagonemia contributes to diabetic hyperglycemia (29,30) in part by driving hepatic expression of the key gluconeogenic enzymes Pepck and G6Pase.”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [29]
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- Authors
- Müller, W. A., Faloona, G. R., & Unger, R. H.
- Affiliations
- Dallas VA Medical Center (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1971-09-01
- Volume
- 50
- Issue
- 9
- Pages
- 1992-1999
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC292125
- OpenAlex
- W1970459847
- Cited by
- 240
- References
- 19
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 1 · 2012: 2
- FWCI
- 43.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucagon secretion, insulin deficiency, hyperglycemia, alpha cells, glucose metabolism, 2-deoxyglucose, mannoheptulose, alloxan-induced diabetes, anti-insulin serum, diazoxide, hyperinsulinemia, pancreatic islets
- MeSH terms
- Animals, Diabetes Mellitus, Diabetes Mellitus, Experimental, Diazoxide, Dogs, Glucagon, Heptoses, Hexoses, Hyperglycemia, Insulin, Insulin Antibodies, Islets of Langerhans, Rats
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