Glucagon-like peptides 1
| Glucagon-like peptides 1 | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 37 amino acids | |
| Precursor | Preproglucagon | |
| Isoforms | 30/31 amino acids | |
| Identifier | ||
| Gene name | GCG | |
| External IDs | ||
The peptide hormone glucagon-like peptide 1 ( GLP-1 ) is next to GIP the most important hormone for the incretin effect (the increased insulin release with enteral compared to parenteral glucose supply). In humans, the active hormone consists of amino acids 7–36 (> 80%) or 7–37 of the preglucagon protein.
The GLP-1 was first described in 1979 by Werner Creutzfeldt's working group at the University of Göttingen .
education
GLP-1 is produced as an intestinal hormone by the neuroendocrine L cells in the ileum and colon in response to glucose in the chyme and released into the bloodstream.
It is broken down by the enzyme dipeptidyl peptidase 4 (DPP 4) within minutes and therefore has to be constantly re-produced.
Effects
- It increases the glucose-dependent release of insulin from the β-cells of the pancreas by binding to G s -coupled receptors . Potassium channels are closed via the protein kinase A signaling path , the resulting depolarization of the cell membrane leads to the opening of voltage-dependent calcium channels . Calcium triggers the fusion of insulin-storing vesicles with the cell membrane. In addition, GLP-1 stimulates the transcription of the insulin gene and the proliferation of the islets of Langerhans .
- It lowers the production of glucagon in the α-cells of the pancreas. (Glucagon releases glucose from the liver.)
- It delays the emptying of gastric contents into the intestines and inhibits gastric juice secretion .
- It promotes satiety by binding to receptors in the area postrema .
- It promotes the release of orexin .
The first two effects prevent excessively high glucose levels in the blood, while the other two effects reduce food intake.
Diabetes therapy with GLP-1
During the analysis of substances from the saliva of the Gila crustacean , the hormone exendin-4 was isolated, which is similar to GLP-1 and how it binds to the receptors of the pancreas, but is not broken down by dipeptidyl peptidase 4. The US pharmaceutical company Amylin genetically developed Exendin-4 and marketed it under the name Exenatid in 2005 as a drug for subcutaneous injection for type II diabetics. As a result, other incretin mimetics were developed and approved as medicinal products.
An alternative are the dipeptidyl peptidase 4 inhibitors , which inhibit the breakdown of GLP-1 and are commercially available as an orally available drug.
Individual evidence
- ↑ UniProt P01275
- ↑ Takeshi Sakurai: The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness . In: Nature Reviews Neuroscience . tape 8 , no. 3 , p. 171-181 , doi : 10.1038 / nrn2092 ( nature.com ).
- ↑ Beatrice R. Amann-Vesti: Clinical Pathophysiology . Georg Thieme Verlag, 2006, ISBN 3-13-449609-7 , p. 77 ( limited preview in Google Book search).
- ↑ Wang Z, Wang RM, Owji AA, Smith DM, Ghatei MA, Bloom SR: Glucagon-like peptide-1 is a physiological incretin in rat . In: J. Clin. Invest. . 95, No. 1, January 1995, pp. 417-21. doi : 10.1172 / JCI117671 . PMID 7814643 . PMC 295450 (free full text).
- ↑ Kim W, Egan JM: The role of incretins in glucose homeostasis and diabetes treatment . In: Pharmacol. Rev. . 60, No. 4, December 2008, pp. 470-512. doi : 10.1124 / pr.108.000604 . PMID 19074620 . PMC 2696340 (free full text).