Glucagon: Role in the Hyperglycemia of Diabetes Mellitus
Abstract
Glucagon suppression by somatostatin reduces or abolishes hyperglycemia in dogs made insulin-deficient by somatostatin, alloxan, or total pancreatectomy. This suggests that the development of severe diabetic hyperglycemia requires the presence of glucagon, whether secreted by pancreatic or newly identified gastrointestinal A cells, as well as a lack of insulin. Glucagon suppression could improve therapeutic glucoregulation in diabetes.
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The multi-receptor agonism approach to weight loss was hindered by commercial considerations of production and formulation, the biological impasse that glucagon potently induces hyperglycemia, and potential dose-limiting cardiovascular liabilities.
“However, this multi-receptor agonism approach to weight loss was hindered by commercial considerations of production and formulation [45], the biological impasse that glucagon potently induces hyperglycemia [56,57], and potential dose-limiting cardiovascular liabilities arising from positive chronotropic actions to influence hemodynamic parameters [58].”
From Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice (2022) · cites this paper as [56]
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 [47]
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 [30]
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 [30]
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- Authors
- Dobbs, R., Sakurai, H., Sasaki, H., Faloona, G., Valverde, I., Baetens, D., Orci, L., & Unger, R.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Hospital Universitario Fundación Jiménez Díaz (ES)
- University of Geneva (CH)
- Venue
- Science
- Published
- 1975-02-14
- Volume
- 187
- Issue
- 4176
- Pages
- 544-547
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2057537453
- Cited by
- 229
- References
- 21
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 7
- FWCI
- 63.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- 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, hyperglycemia, diabetes mellitus, somatostatin, insulin deficiency, alloxan, pancreatic resection, pancreatic A cells, glucoregulation, glucagon suppression
- MeSH terms
- Animals, Arginine, Diabetes Mellitus, Diabetes Mellitus, Experimental, Dogs, Glucagon, Hyperglycemia, Insulin, Oligopeptides, Pancreatectomy, Growth Hormone-Releasing Hormone, Diabetes Complications
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