Exendin-4 protects murine pancreatic β-cells from free fatty acid-induced apoptosis through PI-3K signaling.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the L-cells of the distal intestine that has proliferative and anti-apoptotic actions on the β-cell. METHODS: In this study, exendin-4, a long-acting GLP-1 receptor agonist, was studied as a novel agent to suppress apoptosis in pancreatic β-cells and to protect against free fatty acid (FFA)-induced cytotoxicity. RESULTS: Exendin-4 significantly reduced the percentage of cells that underwent apoptosis when β-cells were exposed to FFA. Exendin-4 increased the levels of P-Akt and Bcl-2 proteins in FFA-induced β-cells, and this effect was blocked by Wortmannin. CONCLUSIONS: These results suggest that phosphoinositide-3 kinase signaling is involved in the modulation of β-cell apoptosis which is induced by exendin-4. Taken together, our findings provide a new mechanism for the modulation of exendin-4 in the pathological processes underlying FFA-induced diabetes mellitus.