ArticleProceedings of the National Academy of Sciences of the United States of America2003
Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 299 papers, 1 of them a synthesis that pooled it.
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Who cites it
299 citing papers in PubMed, 1 synthesis or guideline pooled it, 558 citations in OpenAlex.
- The relationship between glucose and the liver-alpha cell axis - A systematic review.Frontiers in endocrinology · 2022Pooled it
- Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial.Nature medicine · 2022Trial
- Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes.JCI insight · 2018Trial
- Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial.Diabetes, obesity & metabolism · 2018Trial
- Adrenal hormones in the maintenance of glucose homeostasis during prolonged fasting in male glucagon-deficient mice.Journal of diabetes investigation · 2026Article
- One Week Exposure to a Somatostatin Receptor 2 Antagonist (SSTR2a) Enhances Glucagon Counterregulation to Insulin-Induced Hypoglycaemia and Does Not Worsen Glycemia in a Male Rat Model of Insulin-Requiring Type 2 Diabetes.Diabetes, obesity & metabolism · 2026Article
- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
- Loss of Slc39a5 in α-cells impairs glucose metabolism by chronically increasing glucagon.Journal of advanced research · 2026Article
- Prenatal metabolic adversity reprograms insulin-responsive transcription in the developing nucleus accumbens.Molecular metabolism · 2026Article
- Glucagon receptor blockade protects spermatogenesis by enhancing PFKFB3-mediated lactate production in Sertoli cells.Journal of translational medicine · 2026Article
- Alpha-cell glucagon is essential for maintaining β-cell function and identity in adult mice.The Journal of biological chemistry · 2026Article
- Targeting glucagon signaling in metabolic disorders, functional insights from zebrafish receptor knockouts.Cellular and molecular life sciences : CMLS · 2026Article
- Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.The Journal of clinical investigation · 2026Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- Glucagon receptor signaling is indispensable for the healthspan effects of caloric restriction in aging male mice.GeroScience · 2026Article
- Article
- Contractile Effects of Glucagon in Mouse Cardiac Preparations.International journal of molecular sciences · 2025Article
- Intestinal adaptation to cold-induced metabolic demand and feeding requires GLP-1R and GLP-2R signalling.Communications biology · 2025Article
- Hypothalamic Prostaglandins Facilitate Recovery From Severe Hypoglycemia but Exacerbate Recurrent Hypoglycemia in Mice.Diabetes · 2025Article
- Article
239 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Glucagon, the counter-regulatory hormone to insulin, is secreted from pancreatic alpha cells in response to low blood glucose. To examine the role of glucagon in glucose homeostasis, mice were generated with a null mutation of the glucagon receptor (Gcgr(-/-)). These mice display lower blood glucose levels throughout the day and improved glucose tolerance but similar insulin levels compared with control animals. Gcgr(-/-) mice displayed supraphysiological glucagon levels associated with postnatal enlargement of the pancreas and hyperplasia of islets due predominantly to alpha cell, and to a lesser extent, delta cell proliferation. In addition, increased proglucagon expression and processing resulted in increased pancreatic glucogen-like peptide 1 (GLP-1) (1-37) and GLP-1 amide (1-36 amide) content and a 3- to 10-fold increase in circulating GLP-1 amide. Gcgr(-/-) mice also displayed reduced adiposity and leptin levels but normal body weight, food intake, and energy expenditure. These data indicate that glucagon is essential for maintenance of normal glycemia and postnatal regulation of islet and alpha and delta cell numbers. Furthermore, the lean phenotype of Gcgr(-/-) mice suggests glucagon action may be involved in the regulation of whole body composition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.