Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 426, Issue 3, Pages 201-206Publisher
ELSEVIER
DOI: 10.1016/S0014-2999(01)01204-3
Keywords
bezafibrate; PPAR alpha (peroxisome proliferator-activated receptor); pancreatic/duodenal homeobox-1; diazoxide; beta-cell dysfunction
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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 muM 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. (C) 2001 Elsevier Science B.V. All rights reserved.
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