Interrelationship among insulin, glucagon and somatostatin secretory responses to exendin-4 in the perfused rat pancreas.
We have investigated the effect of exendin-4 on insulin, glucagon and somatostatin output in the perfused rat pancreas. At 9 mM glucose, exendin-4 potentiated the insulin and somatostatin responses to arginine and reduced the glucagon response to this amino acid. Thus, this reduction might be thought to be paracrine-mediated through the concomitant increase in insulin and somatostatin concentrations. At 3.2 mM glucose, exendin-4 did not affect insulin secretion, reduced glucagon release and stimulated somatostatin output. Furthermore, exendin-4 reduced glucagon secretion as induced by a glucose decline (from 11 to 3.2 mM) without affecting insulin or somatostatin responses. In summary, exendin-4 stimulated insulin and somatostatin secretion and reduced glucagon release. The glucagonostatic effect of exendin-4 was observed under conditions in which insulin and somatostatin were not affected, thus indicating that exendin-4, per se, inhibits A-cell secretion. Indeed, an additional glucagonostatic effect of exendin-4, mediated by its stimulation of insulin and/or somatostatin secretion, cannot be ruled out.
Silvestre
Ramona A
RA
Hospital Universitario Clínica Puerta de Hierro and Department of Physiology, Universidad Autónoma de Madrid, San Martín de Porres 4, 28035 Madrid, Spain.
Rodríguez-Gallardo
Jovita
J
Egido
Eva M
EM
Marco
J
J
D000818:Animals; D000077270:Exenatide; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology*
D007328:Insulin; D010455:Peptides; D014688:Venoms; D013004:Somatostatin; D005934:Glucagon; D000077270:Exenatide