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Metabolic & GLP-1 · Reference monograph

29-amino-acid hyperglycaemic pancreatic hormone

Reference compound — not available from Purity Peptides. Shown for research context.

Overview

Glucagon is a 29-amino-acid peptide hormone secreted by pancreatic alpha cells. It was discovered in 1923 by Charles Kimball and John Murlin, who identified a hyperglycaemic factor contaminating early pancreatic extracts prepared for insulin research. Its amino acid sequence was determined in 1957, and later work showed that it is processed from proglucagon, the same precursor that gives rise to GLP-1, GLP-2 and oxyntomodulin in the intestine.

Glucagon is the principal counter-regulatory hormone to insulin, defending blood glucose during fasting, exercise and hypoglycaemia. Roger Unger's bihormonal hypothesis argued that excess glucagon, not only insulin deficiency, contributes to hyperglycaemia in diabetes, an idea that continues to shape research. Glucagon is an approved prescription medicine for severe hypoglycaemia and as a diagnostic aid that temporarily inhibits gastrointestinal motility during radiological examinations. In research it is used to study hepatic glucose output, glucagon receptor signalling, amino acid metabolism and counter-regulation, and it is a component of the co-agonist concept now prominent in obesity research.

Mechanism studied

  1. Glucagon
  2. Hepatic GCGR
  3. Glycogenolysis
  4. Blood glucose ↑

Glucagon binds the glucagon receptor (GCGR), a class B G protein-coupled receptor expressed most abundantly in the liver and also in kidney and other tissues. Receptor activation couples to Gs, raising cAMP and activating protein kinase A, which stimulates glycogen phosphorylase and suppresses glycogen synthase to drive glycogenolysis. Over longer periods glucagon promotes gluconeogenesis by inducing enzymes such as PEPCK and glucose-6-phosphatase and by enhancing hepatic amino acid uptake and ureagenesis. Glucagon also increases hepatic fatty acid oxidation and ketogenesis. A liver-alpha cell feedback loop links glucagon signalling to circulating amino acids, which in turn stimulate alpha cells.

Research highlights

  • 01Discovered in 1923 as a hyperglycaemic contaminant of early pancreatic extracts.
  • 02Structural biology studies have resolved the full-length glucagon receptor, informing class B G protein-coupled receptor pharmacology.
  • 03Unger's bihormonal hypothesis placed alpha-cell dysfunction alongside insulin deficiency in diabetes research.
  • 04Studies of GCGR knockout mice and receptor antagonists revealed alpha-cell hyperplasia, helping define the liver-alpha cell axis.
  • 05Open questions include how much glucagon contributes to energy expenditure and how best to balance it in co-agonist designs.

Latest published research

56,837 papers on PubMed →

  1. Future Treatments for Tobacco Dependence

    Jimenez-Ruiz CA et al. · Open respiratory archives · 2027 Mar · PMID 42892933

  2. Integrated LC-MS/MS profiling, network pharmacology and experimental validation reveal inhibition of the IL-6/JAK2/STAT3 pathway by Shenqi Compound in comorbid chronic pancreatitis and type 2 diabetes mellitus

    Su Y et al. · Journal of ethnopharmacology · 2027 Jan 30 · PMID 42562056

  3. Metformin Use Is Associated With Reduced Rates of Primary Nerve Decompression Surgery and Revision in Type 2 Diabetes: A Retrospective Cohort Study

    Abbas Y et al. · Journal of hand surgery global online · 2027 Jan · PMID 42927270

  4. The gut-pancreas axis in chronic pancreatitis: Microbiota-endogenous GLP-1 interactions and candidate repair pathways

    Fan Z et al. · Microbiological research · 2027 Jan · PMID 42854469

  5. Oxidative stress, aging, metabolism, SIRT1, and the gut microbiota: the neurocardiac basis of cognitive loss

    Maiese K et al. · Medical gas research · 2027 Jan 1 · PMID 42545731

  6. Development of Teduglutide purity certified reference material (GBW09342) through amino acid-based isotope dilution mass spectrometry and sulfur-based isotope dilution inductively coupled plasma mass spectrometry

    Li N et al. · Talanta · 2027 Jan 1 · PMID 42385596

  7. Pharmacy students' knowledge and attitudes regarding GLP-1 receptor agonist adverse effects in obesity management: a cross-sectional study

    Khojah AA et al. · The Libyan journal of medicine · 2026 Dec 31 · PMID 42886550

  8. Effect of pasteurized Akkermansia muciniphila MucT on insulin sensitivity, body composition, and GLP-1 production in subjects with metabolic syndrome: impact of low baseline gut Akkermansia levels

    Suenaert P et al. · Gut microbes · 2026 Dec 31 · PMID 42343233

Live feed from PubMed (NCBI) for “Glucagon”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.

Registered studies

1,526 on ClinicalTrials.gov →

From the public ClinicalTrials.gov registry for “Glucagon”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.

Key references

  1. [1]Manufacturer's prescribing information — FDA / EMA / ANVISA
  2. [2]PubMed — reviews on glucagon and severe hypoglycaemia

FAQ

  • Glucagon opposes the actions of insulin. When blood glucose falls, alpha cells release glucagon, which stimulates the liver to release stored glucose and make new glucose. Together with adrenaline, cortisol and growth hormone, it forms the body's defence against hypoglycaemia.

  • Beyond severe hypoglycaemia, glucagon is approved as a diagnostic aid in radiology. Its transient relaxation of gastrointestinal smooth muscle reduces motion during imaging examinations of the stomach and intestine. This application reflects a pharmacological action separate from its effects on the liver.

  • Glucagon and GLP-1 both derive from proglucagon. Alpha cells process proglucagon mainly into glucagon, whereas intestinal L-cells produce GLP-1, GLP-2 and oxyntomodulin. The two hormones act on related but distinct receptors with largely opposing effects on blood glucose.

FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.

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