HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) Supplementary data All Versions of this Article: JOE-08-0397v1 200/2/127    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ropero, A. Articles by Nadal, A. Search for Related Content PubMed PubMed Citation Articles by Ropero, A. Articles by Nadal, A.

A Ropero, Instituto de Bioingenieria, Universidad Miguel Hernandez de Elche, Elche, Spain
P Juan-Pico, Instituto de Bioingenieria, Universidad Miguel Hernandez de Elche, Elche, Spain
A Rafacho, Instituto de Bioingenieria, Universidad Miguel Hernandez de Elche, Elche, Spain
E Fuentes, Instituto de Bioingenieria, Universidad Miguel Hernandez de Elche, Elche, Spain
F Bermudez-Silva, Laboratorio de Medicina Regenerativa, Fundacion IMABIS, Malaga, Spain
E Roche, Instituto de Bioingenieria, Universidad Miguel Hernandez de Elche, Elche, Spain
I Quesada, Instituto de Bioingenieria, Universidad Miguel Hernandez de Elche, Elche, Spain
F Rodriguez de Fonseca, Laboratorio de Medicina Regenerativa, Fundacion IMABIS, Malaga, Spain
A Nadal, Instituto de Bioingenieria, Universidad Miguel Hernandez de Elche, Elche, Spain

Correspondence: Angel Nadal, Email: Nadal{at}umh.es

Abstract

PPARalpha is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. PPARalpha is involved in the regulation of the in vivo triglyceride levels, presumably through its effects on fatty acid and lipoprotein metabolism. Some nuclear receptors have been involved in rapid effects mediated by non-genomic mechanisms. In this paper, we have studied the rapid non-genomic effects of PPARalpha ligands on the intracellular calcium concentration ([Ca2+]i), mitochondrial function, reactive oxygen species (ROS) generation and secretion of insulin in freshly isolated mouse islets of Langerhans. The hypolipidemic fibrate PPARalpha agonist WY-14,643 decreased the glucose-induced calcium oscillations in intact islets. This effect was mimicked by the synthetic agonist GW7647 and the endogenous agonist oleylethanolamide (OEA). The WY-14,643 action was rapid in onset (5 minutes) and was still produced in the presence of protein and mRNA synthesis inhibitors, cycloheximide and actynomicin D. This suggests that it is independent of gene transcription. In addition, WY-14,623 impaired mitochondrial function, increased ROS formation and decreased insulin release. PPARalpha is present in beta-cells, mainly in the cytosol and nucleus, with a small subpopulation localized in the plasma membrane. However, the presence of PPARalpha ligand effects in mice bearing a disrupted Pparalpha gene rises the possibility that the rapid effects of the agonists in pancreatic beta-cells are independent of the receptor. We conclude that PPARalpha agonists produce a decrease in glucose-induced [Ca2+]i signals and insulin secretion in beta-cells through a rapid, non-genomic mechanism.