Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (678 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Glucagon (1-29); Hyperglycemic-Glycogenolytic Factor; Hyperglycemic Glycogenolytic Factor; HG-Factor; HG Factor; Glukagon; Proglucagon (33-61).
Where it fits in the MeSH classification
- Broader topics
- Proglucagon
- See also
- Receptors, Glucagon
Related concepts
- Glucagon-Like Peptides
- Pancreatic Alpha Cells
- Blood Glucose
Research landscape
PubMed indexes 26,689 records tagged with the MeSH heading “Glucagon” (counts retrieved 2026-10-31). 1,596 of them (6.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 19,479 records.
Reviews account for 2,236 records (8.4%) and meta-analyses for 26. Randomized controlled trials number 1,023 (3.8%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 19,479 |
| 2000-2009 | 3,107 |
| 2010-2019 | 2,507 |
| 2020 onward | 1,596 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,236 | 8.4% |
| Meta-analyses | 26 | 0.1% |
| Randomized controlled trials | 1,023 | 3.8% |
Method: PubMed query "Glucagon"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice | 2022 | Research article Design not recorded in structured metadata | 123 | cc by PMID 35809773 · DOI · PMC9305623 |
| Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes | 2020 | Research article Design not recorded in structured metadata | 97 | cc by PMID 32312960 · DOI · PMC7171169 |
| Alpha cell regulation of beta cell function | 2020 | Review article Design not recorded in structured metadata | 88 | cc by PMID 32894317 · DOI · PMC7476996 |
| Adipose Tissue, at the Core of the Action of Incretin and Glucagon-Based Anti-Obesity Drugs | 2025 | Review article Design not recorded in structured metadata | 5 | cc by PMID 40892365 · DOI · PMC12405374 |
Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice [1]
Abstract reading summary — source excerpts
- Opening excerpt
- ObjectivePharmacological strategies that engage multiple mechanisms-of-action have demonstrated synergistic benefits for metabolic disease in preclinical models.
- Closing excerpt
- ConclusionsThese pre-clinical data suggest unimolecular poly-pharmacology as an effective means to target multiple mechanisms contributing to obesity and further implicate GcgR activation as the differentiating factor between incretin receptor mono- or dual-agonists and triagonists.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (198 words)
ObjectivePharmacological strategies that engage multiple mechanisms-of-action have demonstrated synergistic benefits for metabolic disease in preclinical models. One approach, concurrent activation of the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon (Gcg) receptors (i.e. triagonism), combines the anorectic and insulinotropic activities of GLP-1 and GIP with the energy expenditure effect of glucagon. While the efficacy of triagonism in preclinical models is known, the relative contribution of GcgR activation remains unassessed. This work aims to addresses that central question.MethodsHerein, we detail the design of unimolecular peptide triagonists with an empirically optimized receptor potency ratio. These optimized peptide triagonists employ a protraction strategy permitting once-weekly human dosing. Additionally, we assess the effects of these peptides on weight-reduction, food intake, glucose control, and energy expenditure in an established DIO mouse model compared to clinically relevant GLP-1R agonists (e.g. semaglutide) and dual GLP-1R/GIPR agonists (e.g. tirzepatide).ResultsOptimized triagonists normalize body weight in DIO mice and enhance energy expenditure in a manner superior to that of GLP-1R mono-agonists and GLP-1R/GIPR co-agonists.ConclusionsThese pre-clinical data suggest unimolecular poly-pharmacology as an effective means to target multiple mechanisms contributing to obesity and further implicate GcgR activation as the differentiating factor between incretin receptor mono- or dual-agonists and triagonists.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35809773 · DOI · PMC9305623
Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Glucagon is released from pancreatic α-cells to activate pathways that raise blood glucose.
- Closing excerpt
- Thus, elevated glucagon in human T2D may reflect α-cell insensitivity to paracrine inhibition at hyperglycemia.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Glucagon is released from pancreatic α-cells to activate pathways that raise blood glucose. Its secretion is regulated by α-cell-intrinsic glucose sensing and paracrine control through insulin and somatostatin. To understand the inadequately high glucagon levels that contribute to hyperglycemia in type-2 diabetes (T2D), we analyzed granule behavior, exocytosis and membrane excitability in α-cells of 68 non-diabetic and 21 T2D human donors. We report that exocytosis is moderately reduced in α-cells of T2D donors, without changes in voltage-dependent ion currents or granule trafficking. Dispersed α-cells have a non-physiological V-shaped dose response to glucose, with maximal exocytosis at hyperglycemia. Within intact islets, hyperglycemia instead inhibits α-cell exocytosis, but not in T2D or when paracrine inhibition by insulin or somatostatin is blocked. Surface expression of somatostatin-receptor-2 is reduced in T2D, suggesting a mechanism for the observed somatostatin resistance. Thus, elevated glucagon in human T2D may reflect α-cell insensitivity to paracrine inhibition at hyperglycemia.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32312960 · DOI · PMC7171169
Alpha cell regulation of beta cell function [3]
Abstract reading summary — source excerpts
- Opening excerpt
- The islet of Langerhans is a complex endocrine micro-organ consisting of a multitude of endocrine and non-endocrine cell types.
- Closing excerpt
- Graphical abstract.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (197 words)
The islet of Langerhans is a complex endocrine micro-organ consisting of a multitude of endocrine and non-endocrine cell types. The two most abundant and prominent endocrine cell types, the beta and the alpha cells, are essential for the maintenance of blood glucose homeostasis. While the beta cell produces insulin, the only blood glucose-lowering hormone of the body, the alpha cell releases glucagon, which elevates blood glucose. Under physiological conditions, these two cell types affect each other in a paracrine manner. While the release products of the beta cell inhibit alpha cell function, the alpha cell releases factors that are stimulatory for beta cell function and increase glucose-stimulated insulin secretion. The aim of this review is to provide a comprehensive overview of recent research into the regulation of beta cell function by alpha cells, focusing on the effect of alpha cell-secreted factors, such as glucagon and acetylcholine. The consequences of differences in islet architecture between species on the interplay between alpha and beta cells is also discussed. Finally, we give a perspective on the possibility of using an in vivo imaging approach to study the interactions between human alpha and beta cells under in vivo conditions. Graphical abstract.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32894317 · DOI · PMC7476996
Adipose Tissue, at the Core of the Action of Incretin and Glucagon-Based Anti-Obesity Drugs [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Purpose of the reviewThis review summarizes recent evidence highlighting the specific role of adipose tissue in the systemic effects of incretin agonist-based drugs used in the treatment of obesity.
- Closing excerpt
- The direct and indirect actions of incretin-based anti-obesity drugs, which modify the properties of adipose tissue, are emerging as key contributors to the systemic health benefits of these treatments.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (133 words)
Purpose of the reviewThis review summarizes recent evidence highlighting the specific role of adipose tissue in the systemic effects of incretin agonist-based drugs used in the treatment of obesity.Recent findingsThe development of incretin agonist-based drugs has achieved unprecedented success in the pharmacological treatment of obesity and the improvement of obesity-related comorbidities. While initially shown to significantly reduce adipose tissue through decreased food intake, incretin-based therapy is also increasingly reported to alter the properties of adipose tissue. Recent experimental and human studies indicate that these anti-obesity drugs induce significant changes in the metabolism and inflammatory state of adipose tissue, while also promoting its thermogenic plasticity. The direct and indirect actions of incretin-based anti-obesity drugs, which modify the properties of adipose tissue, are emerging as key contributors to the systemic health benefits of these treatments.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40892365 · DOI · PMC12405374
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Glucagon and regulation of glucose metabolism [5]
- Research article The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion [6]
- Research article Physiology of proglucagon peptides: role of glucagon and GLP-1 in health and disease [7]
- Research article Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans [8]
- Research article Cell and molecular biology of the incretin hormones glucagon-like peptide-I and glucose-dependent insulin releasing polypeptide [9]
- Research article Glucagon-like peptides [10]
References
- Knerr PJ, Mowery SA, Douros JD, Premdjee B, Hjøllund KR, He Y, et al.. Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice. . 2022. PMID 35809773 · DOI · PMC9305623
- Omar-Hmeadi M, Lund PE, Gandasi NR, Tengholm A, Barg S. Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes. . 2020. PMID 32312960 · DOI · PMC7171169
- Moede T, Leibiger IB, Berggren PO. Alpha cell regulation of beta cell function. . 2020. PMID 32894317 · DOI · PMC7476996
- Villarroya F, Peyrou M, Giralt M. Adipose Tissue, at the Core of the Action of Incretin and Glucagon-Based Anti-Obesity Drugs. . 2025. PMID 40892365 · DOI · PMC12405374
- Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2003. PMID 12626323 · DOI
- MacDonald PE, El-Kholy W, Riedel MJ, Salapatek AM, Light PE, Wheeler MB. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes. 2002. PMID 12475787 · DOI
- Sandoval DA, D'Alessio DA. Physiology of proglucagon peptides: role of glucagon and GLP-1 in health and disease. Physiol Rev. 2015. PMID 25834231 · DOI
- Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004. PMID 15271645 · DOI
- Fehmann HC, Göke R, Göke B. Cell and molecular biology of the incretin hormones glucagon-like peptide-I and glucose-dependent insulin releasing polypeptide. Endocr Rev. 1995. PMID 7671853 · DOI
- Drucker DJ. Glucagon-like peptides. Diabetes. 1998. PMID 9519708 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.