Central Laboratory, Provincial Hospital affiliated to Shandong University, No. 324, Jing 5 Road, Jinan, 250021, China.
J Endocrinol Invest. 2010 Jul-Aug;33(7):465-71. doi: 10.1007/BF03346626. Epub 2010 Jan 22.
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.
已知 AMP 激活的蛋白激酶 (AMPK) 的激活可减弱胰岛β细胞中葡萄糖刺激的胰岛素分泌 (GSIS)。然而，其潜在机制尚不清楚。本研究的目的是研究 AMPK 激活对胰岛素分泌的影响，并确定过氧化物酶体增殖物激活受体 (PPAR) 是否参与了对 INS-1 细胞的作用。
用 AMPK 的激活剂 (AICAR) 或抑制剂 (Compound C) 以及 PPAR 的抑制剂 [MK886 和双酚 A 二缩水甘油醚 (BADGE)] 处理 INS-1 细胞（胰岛素瘤细胞系），进行不同时间的处理。
AICAR 诱导的 AMPK 激活显著减弱了 GSIS 以及胰岛素含量。同时，AMPK 激活增加了 PPARalpha 和 PPARgamma 的 mRNA 水平。然而，就 DNA 结合而言，AMPK 激活仅上调了 PPARgamma，并且可以用 AMPK 抑制剂来减少这种上调。此外，AICAR 诱导的胰岛素分泌抑制可以被 PPARgamma 抑制剂 BADGE 抵消，但不能被 PPARalpha 抑制剂抵消。
AICAR 诱导的葡萄糖刺激的胰岛素分泌减少主要与 PPARgamma 的变化相关。
