Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas.
Kisspeptins are a family of peptides encoded by the KISS1 gene, which binds to G-protein-coupled receptor (GPR54), an orphan GPR54 related to galanin receptors. Endogenous forms composed of 54, 14, and 13 amino acids have been identified. Kisspeptin and GPR54 mRNAs have been detected in pancreatic B and A cells. Furthermore, kisspeptin-54 has been shown to slightly stimulate the last phase of glucose-induced insulin secretion in mouse and human islets and to inhibit insulin release in MIN6 cells. We have investigated the effect of kisspeptin-13 on insulin, glucagon, and somatostatin secretion. The study was performed in the perfused rat pancreas. Glucose, arginine, carbachol, and exendin-4 were used as secretagogues. Hormones were measured by RIA. Kisspeptin-13 reduced glucose-induced insulin secretion in a dose-dependent manner (IC(50)=1.2 nM) and inhibited the insulin responses to both carbachol and exendin-4. Kisspeptin-13 blocked arginine-induced insulin secretion without affecting the glucagon or somatostatin responses to this amino acid, thus indicating that kisspeptin-13 influences B cells directly, rather than through an A- or D-cell paracrine effect. The reduction of the insulin response to exendin-4 induced by kisspeptin-13 was also observed in pertussis toxin-treated rats, thus suggesting an inhibition independent of G(i) proteins. In view of the potent insulinostatic effect of kisspeptin-13, it is tempting to speculate that kisspeptins may be implicated in the regulation of B-cell secretion.
Silvestre
R A
RA
Hospital Universitario Puerta de Hierro and Department of Physiology, Medical School, Universidad Autónoma de Madrid, San Martín de Porres 4, 28035 Madrid, Spain. rsilvestre.hpth@salud.madrid.org
Egido
E M
EM
Hernández
R
R
Marco
J
J
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000078790:Insulin Secretion; D059648:Kisspeptins; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology
D007328:Insulin; D007329:Insulin Antagonists; C491406:Kiss1 protein, rat; D059648:Kisspeptins; D010455:Peptides; D011506:Proteins; D014688:Venoms; D013004:Somatostatin; D002217:Carbachol; D005934:Glucagon; D001120:Arginine; D000077270:Exenatide; D037342:Pertussis Toxin