Effects of bezafibrate on beta-cell function of rat pancreatic islets

Bezafibrate is an activator of peroxisome proliferator-activated receptors (PPAR) alpha. The present study was performed to investigate the effects of bezafibrate and the PPAR alpha activator, 4-Cholro-6-(2.3-xylidino)-2-pyrimidin-ylthio acetic acid (WY14643), on the beta-cell function of rat pancreatic islets in vitro. In islets cultured with 300 microM bezafibrate or WY14643 for 8 h, a low glucose concentration induced insulin release and increased the levels of mRNA for PPAR alpha, acyl CoA oxidase, carnitine palmitoyl transferase-1, pyruvate dehydrogenase E1 alpha or pyruvate carboxylase. In contrast, after a 48-h culture period, a high glucose concentration induced insulin release and islet insulin content, but decreased the levels of mRNA for glucose transporter-2 (GLUT-2), preproinsulin or pancreatic/duodenal homeobox-1. Diazoxide, the KATP channel opener, restored these responses. We conclude that bezafibrate enhances insulin release through the activation of PPAR alpha gene expression during a short culture period, whereas it may contribute to beta-cell dysfunction through the mechanism of "excessive stimulation" during longer culture periods.