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.
Yoshikawa
H
H
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi, Fukuoka 812-0082, Japan. e-yoshi@xb4.so-net.ne.jp
Tajiri
Y
Y
Sako
Y
Y
Hashimoto
T
T
Umeda
F
F
Nawata
H
H
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D011766:Pyruvate Carboxylase / Q000235:genetics; D030481:Pyruvate Dehydrogenase (Lipoamide); D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics
D007328:Insulin; D011743:Pyrimidines; D011768:Pyruvate Dehydrogenase Complex; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C006253:pirinixic acid; D010088:Oxidoreductases; D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit; C418542:acyl CoA oxidase 3; D002334:Carnitine O-Palmitoyltransferase; D011766:Pyruvate Carboxylase; D005947:Glucose; D001629:Bezafibrate