Horm Metab Res 2004; 36(9): 595-600
DOI: 10.1055/s-2004-825921
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Exendin-4 Dose-dependently Stimulates Somatostatin and Insulin Secretion in Perfused Rat Pancreas

E.  M.  Egido1 , R.  A.  Silvestre1 , R.  Hernández1 , J.  Marco1
  • 1Hospital Universitario Puerta de Hierro and Department of Physiology, Medical School, Universidad Autónoma de Madrid, San Martín de Porres 4, 28035 Madrid, Spain
Further Information

Publication History

Received 15 December 2003

Accepted after revision 6 May 2004

Publication Date:
05 October 2004 (online)

Abstract

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 (R2 = 0.9954 and R2 = 0.9973, respectively; p < 0.01) and the EC50 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.

References

R. A. Silvestre, Ph. D.

Hospital Universitario Puerta de Hierro and Department of Physiology, Medical School, Universidad Autónoma de Madrid

San Martín de Porres, 4 · 28035 Madrid · Spain

Phone: +34 (91) 316 22 40, Ext. 5463

Fax: +34 (91) 373 76 67

Email: rsilvestre.hpth@salud.madrid.org