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Structural model of glucagon ( ball and stick model )

Existing structural data: 1bh0, 1d0r, 1nau

Properties of human protein
Mass / length primary structure 29 amino acids, 3483 Da
Precursor Preproglucagon
Gene names GCG  ; GLP1; GLP2; GRPP
External IDs
Drug information
ATC code H04 AA01
DrugBank DB00040
Parent taxon Vertebrates
human mouse
Entrez 2641 14526
Ensemble ENSG00000115263 ENSMUSG00000000394
UniProt P01275 P55095
Refseq (mRNA) NM_002054 NM_008100
Refseq (protein) NP_002045 NP_032126
Gene locus Chr 2: 162.71 - 162.71 Mb Chr 2: 62.28 - 62.28 Mb
PubMed search 2641 14526

Glucagon (also known as glucagon ) is a peptide hormone whose main effect is to increase blood sugar levels by stimulating the formation of high-energy glucose from glycogen in the liver. It is formed from the precursors preglucagon and preproglucagon in the islets of Langerhans of the pancreas (α-islet cells). When blood sugar drops , but also after a protein-rich meal, glucagon is released from the pancreas into the bloodstream and transported there freely. This hormone is an antagonist of insulin in its effect on glucose, protein and fatty acid metabolism . Glucagon is absorbed by the liver and inactivated by cleavage.


The existence of the pancreatic hormone glucagon as a hyperglycemic factor was first postulated in 1923 by John Raymund Murlin . But it was not until 1953 that Anne-Marie Staub was able to obtain the pure substance. The sequencing recorded below was developed by William Wallis Bromer in 1956 . In 1960, Ronald Ralph Tuttle and Alfed Emil Farah researched and demonstrated positive effects on cardiac output . In the past, the glucagon v. a. used in cardiogenic shock.


From the glucagon precursor protein of 180 amino acids, 7 other peptides are formed in addition to glucagon - glicentin, glicentin-related polypeptide (GRPP), oxyntomodulin , glucagon-like peptide 1 (GLP-1, incretin hormone), glucagon-like peptide 1 ( 7-37), glucagon-like peptide 1 (7-36), glucagon-like peptide 2 (GLP-2). The primary structure of human glucagon consists of 29 amino acids with a molecular mass of 3483 Da . The primary structure is: His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val- Gln-Trp-Leu-Met-Asn-Thr.

Glucagon secretion

Glucagon (red) production in the Langerhans Islands

With a normal diet, the secretion of glucagon remains relatively constant compared to that of insulin . The main stimuli for increased secretion are hypoglycaemia (low blood sugar level), protein-rich meals, infusion of amino acids (e.g. arginine , alanine ), long-term vigorous physical activity and stress . In hypoglycaemia, glucagon secretion can be increased up to four times. Stimulation occurs through β-adrenoreceptors. Its release is inhibited by insulin, somatostatin and GLP1 . GIP increases the release of glucagon.

Mechanism of action

Glucagon is the antagonist of insulin. While insulin promotes glycogen synthesis , the release of glucagon results in the breakdown of glycogen . Glucagon works by binding to a G protein-coupled receptor . The G s protein activated thereby stimulates the adenylate cyclase ( EC ). The enzymes for glucose and fat metabolism are activated by cAMP . As a priority effect that is glycogen phosphorylase ( EC ) phosphorylated that the glycogen stimulates glycogen synthesis and inhibits.  

Regulation of glycogen metabolism. Adrenaline (muscle) or glucagon (liver) activate a G protein-coupled receptor (GPCR) to which a G s protein is docked. GDP has bound its α-subunit , which is then exchanged with GTP . This releases the α-subunit from the receptor and activates an adenylyl cyclase (AC). The resulting cAMP activates a protein kinase A (PKA), which in turn catalyzes the phosphorylation of a phosphorylase kinase (PPK). The kinase thus stimulated catalytically activates a glycogen phosphorylase (PYG), which catalyzes the breakdown of glycogen to glucose-1-phosphate . Protein kinase A simultaneously phosphorylates a UDP glycogen synthase (GYS), which is thereby inactivated and can no longer catalyze the reverse reaction.

Glucagon not only stimulates glycogenolysis, but also the new synthesis of glucose ( gluconeogenesis ) from amino acids. So glucagon has a protein catabolic effect, which leads to an increase in urea in the blood. In addition, fat-digesting enzymes ( lipases ) are activated via cAMP , which results in an increase in fatty acids in the blood.


Glucagon is used for immobilization of the intestine is inserted and also in this function as intravenously administrable drug used. The active ingredient is also used as an antidote for poisoning with beta blockers and calcium channel blockers . It is also used in gastric x-ray to better assess the mucous membrane.

At the heart, glucagon causes not only an increase in the heart rate but also a short-term increase in the contraction force of the heart muscle.

In addition, many diabetics who require insulin have an emergency kit with glucagon and a solvent, which is injected subcutaneously or intramuscularly by a trained helper in severe hypoglycemia with unconsciousness after dissolution of the powder substance and which is supposed to increase the blood sugar level via the mechanism of action described above. Glucagon is sold by the manufacturer Novo Nordisk under the trade name GlucaGen ® .

In October 2019, the CHMP of the European approval authority (EMA) spoke out in favor of the approval of a completely new type of glucaone-containing dosage form in which the hormone can be administered through the nose. Eli Lilly has applied for approval . The intended trade name is Baqsimi . As a rule, approval is granted on such a recommendation.

For a study carried out in 2010, an insulin pump was developed which, in addition to the insulin ampoule, also contained a glucagon ampoule. With constant glucose measurement in a closed-loop system (blood glucose measurement and dose delivery take place automatically), glucagon was delivered via the pump if there was a risk of hypoglycaemia. As a result, fewer and shorter-lasting hypoglycaemia occurred.

Glucagon test (C-peptide)

There is a glucagon test that is rarely used in everyday medical practice. It is used to test the stimulability of the β cells of the pancreas (functional reserve) to differentiate between type I and type II diabetes.


  1. Blood sampling for the determination of C-peptide basal. Administration of 1 mg glucagon iv
  2. Blood sampling 6 min. after glucagon to measure the stimulated C-peptide level (β-cell functional reserve).


  • An increase in the C-peptide of at least 0.5 nmol / l and / or more than 1.0 nmol / l indicates functional β cells.
  • Blood glucose should always be determined in order to determine the degree of pre-stimulation of the β cells.

See also

Web links

Individual evidence

  1. ^ Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2., revised. and exp. Edition. Knowledge Verl-Ges, Stuttgart 2005, ISBN 3-8047-2113-3 , p. 164 .
  2. a b GCG - Glucagon precursor - Homo sapiens (Human) - GCG gene & protein. In: June 20, 2018, accessed May 24, 2018 .
  3. Mikkel Bring Christensen: Glucose-dependent insulinotropic polypeptide: effects on insulin and glucagon secretion in humans . In: Danish Medical Journal . tape 63 , no. April 4 , 2016, ISSN  2245-1919 , PMID 27034187 .
  4. Swiss Toxicological Information Center, antidote monograph for glucagon (PDF; 39 kB) .
  5. Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , p. 57.
  6. First non-injectable treatment for severe low blood sugar levels , PM EMA of 18 October 2019 called on October 29, 2019
  7. The insulin pump with additional glucagon , (accessed on June 19, 2011).