Exendin-4 dose-dependently stimulates somatostatin and insulin secretion in perfused rat pancreas.
We have investigated the effect of exendin-4, a GLP-1 analogue, on somatostatin and insulin secretion in perfused rat pancreas. At constant glucose concentration within the type 2 diabetic range (9 mM), exendin-4 stimulated somatostatin and insulin secretion in a dose-dependent manner. Dose-response curves were sigmoidal (R (2) = 0.9954 and R (2) = 0.9973, respectively; p < 0.01) and the EC (50) was 4.3 nM for somatostatin secretion and 1.4 nM for insulin secretion. Exendin-4 stimulated somatostatin output at low (3.2 mM), normal (5.5 mM) and high (9 mM) glucose concentrations, while the insulinotropic effect of exendin-4 was not found at low glucose levels. On the other hand, exendin-4 potentiated somatostatin and insulin responses to an increase in perfusate glucose levels, and to arginine and carbachol. Finally, the insulinotropic effect of exendin-4 was maintained in the absence of a somatostatin response as induced by cysteamine pretreatment, indicating a direct effect of exendin-4 on the B-cell. In summary, exendin-4 behaves as a general stimulatory agent of both insulin and somatostatin release in the perfused rat pancreas. Given that exendin-4 has also been shown to increase gastric somatostatin secretion, it is tempting to speculate that exendin-4 might behave as a general stimulator of D-cell function in other tissues, a point worthy of further investigation.
Hospital Universitario Puerta de Hierro and Department of Physiology, Medical School, Universidad Autónoma de Madrid, San Martín de Porres 4, 28035 Madrid, Spain.
E M
EM
Egido
R A
RA
Silvestre
R
R
Hernández
J
J
Marco
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003543:Cysteamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism*; D019864:Somatostatin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D014688:Venoms / Q000008:administration & dosage* / Q000494:pharmacology
D007328:Insulin; D010455:Peptides; D014688:Venoms; D013004:Somatostatin; D003543:Cysteamine; D002217:Carbachol; D001120:Arginine; D000077270:Exenatide; D005947:Glucose