ArticleJCI insight2019
Glucagon lowers glycemia when β-cells are active.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
113 citing papers in PubMed, 159 citations in OpenAlex.
- Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy).Diabetes, obesity & metabolism · 2023Trial
- SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans.Diabetes · 2021Trial
- Nutrient and non-nutrient regulators of insulin secretion.Nature reviews. Endocrinology · 2026Review
- 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
- Somatostatin receptors shape insulin and glucagon output within the pancreatic islet in mice through direct and paracrine effects.Diabetologia · 2026Article
- Metabolic state determines the brain and direct islet effects of liraglutide on enhanced insulin secretion.Diabetologia · 2026Article
- Dysregulated glucagon signaling contributes to hypoglycemia after vertical sleeve gastrectomy in mice.Molecular metabolism · 2026Article
- Dose-Response Effect of Glucagon on Glucose, Beta-Cell Secretion and Metabolism in Healthy Individuals.Diabetes, obesity & metabolism · 2026Article
- Article
- Markers of beta cell and alpha cell mass in human stem cell-generated implants with glycemic control at human setpoint.Stem cells translational medicine · 2026Article
- Alpha-cell glucagon is essential for maintaining β-cell function and identity in adult mice.The Journal of biological chemistry · 2026Article
- Article
- Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders.Clinical and molecular hepatology · 2026Review
- Ectopic, hepatic GLP-1R agonism enhances the weight loss efficacy of GLP-1 analogues.Molecular metabolism · 2026Article
- Article
- Prolonged Somatostatin Receptor 2 Antagonism Enhances Glucagon Response to Hypoglycemia in Male Diabetic Rats.Endocrinology · 2026Article
- Somatostatin Receptors Shape Insulin and Glucagon Output within the Pancreatic Islet through Direct and Paracrine Effects.bioRxiv : the preprint server for biology · 2025Article
- Clinical characteristics of Japanese Americans with normal glucose tolerance with 1-h hyperglycemia: A cross-sectional study.Journal of diabetes investigation · 2025Article
- α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion.Science advances · 2025Article
- MASLD development: From molecular pathogenesis toward therapeutic strategies.Chinese medical journal · 2025Review
53 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
9 authors at 2 institutions in 1 country.
Funding
Abstract
Glucagon and insulin are commonly believed to have counteracting effects on blood glucose levels. However, recent studies have demonstrated that glucagon has a physiologic role to activate β-cells and enhance insulin secretion. To date, the actions of glucagon have been studied mostly in fasting or hypoglycemic states, yet it is clear that mixed-nutrient meals elicit secretion of both glucagon and insulin, suggesting that glucagon also contributes to glucose regulation in the postprandial state. We hypothesized that the elevated glycemia seen in the fed state would allow glucagon to stimulate insulin secretion and reduce blood glucose. In fact, exogenous glucagon given under fed conditions did robustly stimulate insulin secretion and lower glycemia. Exogenous glucagon given to fed Gcgr:Glp1rβcell-/- mice failed to stimulate insulin secretion or reduce glycemia, demonstrating the importance of an insulinotropic glucagon effect. The action of endogenous glucagon to reduce glycemia in the fed state was tested with administration of alanine, a potent glucagon secretagogue. Alanine raised blood glucose in fasted WT mice or fed Gcgr:Glp1rβcell-/- mice, conditions where glucagon is unable to stimulate β-cell activity. However, alanine given to fed WT mice produced a decrease in glycemia, along with elevated insulin and glucagon levels. Overall, our data support a model in which glucagon serves as an insulinotropic hormone in the fed state and complements rather than opposes insulin action to maintain euglycemia.
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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.