ArticleMolecular metabolism2016
Glucagon receptor gene deletion in insulin knockout mice modestly reduces blood glucose and ketones but does not promote survival.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- A first-in-human pharmacodynamic and pharmacokinetic study of a fully human anti-glucagon receptor monoclonal antibody in normal healthy volunteers.Diabetes, obesity & metabolism · 2018Trial
- Glucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence.The Journal of endocrinology · 2024Review
- The impact of glucagon to support postabsorptive glucose flux and glycemia in healthy rats and its attenuation in male Zucker diabetic fatty rats.American journal of physiology. Endocrinology and metabolism · 2024Article
- Rise in fasting and dynamic glucagon levels in children and adolescents with obesity is moderate in subjects with impaired fasting glucose but accentuated in subjects with impaired glucose tolerance or type 2 diabetes.Frontiers in endocrinology · 2024Article
- 100 years of glucagon and 100 more.Diabetologia · 2023Review
- The past, present, and future physiology and pharmacology of glucagon.Cell metabolism · 2022Review
- Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia.Frontiers in endocrinology · 2021Review
- Global Transcriptomic Analysis of Zebrafish Glucagon Receptor Mutant Reveals Its Regulated Metabolic Network.International journal of molecular sciences · 2020Article
- Leptin Receptors in RIP-CreFrontiers in endocrinology · 2020Article
- Deletion of the glucagon receptor gene before and after experimental diabetes reveals differential protection from hyperglycemia.Molecular metabolism · 2018Article
- Problem or solution: The strange story of glucagon.Peptides · 2018Review
- Lipid nanoparticle delivery of glucagon receptor siRNA improves glucose homeostasis in mouse models of diabetes.Molecular metabolism · 2017Article
- Regulation of hepatic glucose metabolism in health and disease.Nature reviews. Endocrinology · 2017Review
- The glucoregulatory actions of leptin.Molecular metabolism · 2017Review
- Article
- Insulin and Glucagon: Partners for Life.Endocrinology · 2017Review
- Glucagon receptor inhibition normalizes blood glucose in severe insulin-resistant mice.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveIt has been thought that the depletion of insulin is responsible for the catabolic consequences of diabetes; however, evidence suggests that glucagon also plays a role in diabetes pathogenesis. Glucagon suppression by glucagon receptor (Gcgr) gene deletion, glucagon immunoneutralization, or Gcgr antagonist can reverse or prevent type 1 diabetes in rodents suggesting that dysregulated glucagon is also required for development of diabetic symptoms. However, the models used in these studies were rendered diabetic by chemical- or immune-mediated β-cell destruction, in which insulin depletion is incomplete. Therefore, it is unclear whether glucagon suppression could overcome the consequence of the complete lack of insulin.
methodsTo directly test this we characterized mice that lack the Gcgr and both insulin genes (GcgrKO/InsKO).
resultsIn both P1 pups and mice that were kept alive to young adulthood using insulin therapy, blood glucose and plasma ketones were modestly normalized; however, mice survived for only up to 6 days, similar to GcgrHet/InsKO controls. In addition, Gcgr gene deletion was unable to normalize plasma leptin levels, triglycerides, fatty acids, or hepatic cholesterol accumulation compared to GcgrHet/InsKO controls.
conclusionTherefore, the metabolic manifestations associated with a complete lack of insulin cannot be overcome by glucagon receptor gene inactivation.
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Registered trials
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