Suppression effects of AICAR on insulin secretion involved in peroxisome proliferator-activated receptor gamma changes in INS-1 cells.

Journal of Endocrinological Investigation
H GuoL Gao

Abstract

AMP-activated protein kinase (AMPK) activation is known to attenuate glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells. However, the underlying mechanisms are poorly understood. The purpose of this study was to examine the effects of AMPK activation on insulin secretion and to determine whether peroxisome proliferator-activated receptors (PPAR) are involved in the effects on INS-1 cells. INS-1 cells, insulinoma cell lines, were treated with an activator (AICAR) or inhibitor (Compound C) of AMPK as well as inhibitors of PPAR [MK886 and biphenol A diglycidyl ether (BADGE)] for different treatment times. AICAR-induced AMPK activation significantly attenuated GSIS as well as insulin content. Meanwhile, AMPK activation increased the mRNA levels of both PPARalpha and PPARgamma. However, with regard to DNA binding, AMPK activation upregulated PPARgamma only, and it was possible to reduce the increment with the AMPK inhibitor. Moreover, the AICAR-induced suppression of insulin secretion can be counteracted by the PPARgamma inhibitor, BADGE but not the PPARalpha inhibitor. AICAR-induced glucose-stimulated insulin secretion reduction correlates mainly with PPARgamma changes.

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