Effect of obestatin on insulin, glucagon and somatostatin secretion in the perfused rat pancreas.
Obestatin is a 23-amino acid peptide derived from preproghrelin, purified from stomach extracts and detected in peripheral plasma. In contrast to ghrelin, obestatin has been reported to inhibit appetite and gastric motility. However, these effects have not been confirmed by some groups. Obestatin was originally proposed to be the ligand for GPR39, a receptor related to the ghrelin receptor subfamily, but this remains controversial. Obestatin and GPR39 are expressed in several tissues, including pancreas. We have investigated the effect of obestatin on islet cell secretion in the perfused rat pancreas. Obestatin, at 10 nM, inhibited glucose-induced insulin secretion, while at 1 nM, it potentiated the insulin response to glucose, arginine and tolbutamide. The potentiated effect of obestatin on glucose-induced insulin output was not observed in the presence of diazoxide, an agent that activates ATP-dependent K(+) channels, thus suggesting that these channels might be sensitive to this peptide. Obestatin failed to significantly modify the glucagon and somatostatin responses to arginine, indicating that its stimulation of insulin output is not mediated by an alpha- or delta-cell paracrine effect. Our results allow us to speculate about a role of obestatin in the control of beta-cell secretion. Furthermore, as an insulinotropic agent, its potential antidiabetic effect may be worthy of investigation.
Egido
Eva M
EM
Department of Physiology, Medical School, Universidad Autónoma de Madrid, San Martín de Porres 4, 28035 Madrid, Spain.
Hernández
Raquel
R
Marco
José
J
Silvestre
Ramona A
RA
D000818:Animals; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D036361:Peptide Hormones / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism*
D007328:Insulin; D036361:Peptide Hormones; C505798:obestatin, rat; D013004:Somatostatin; D005934:Glucagon