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


METHODS
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.


RESULTS
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.


CONCLUSIONS
AICAR-induced glucose-stimulated insulin secretion reduction correlates mainly with PPARgamma changes.
Guo
H
H
Central Laboratory, Provincial Hospital affiliated to Shandong University, No. 324, Jing 5 Road, Jinan, 250021, China. gaoling1@medmail.com.cn
Zhang
X J
XJ
Wang
F
F
Wang
Y
Y
Shen
Y
Y
Zhao
J J
JJ
Gao
L
L
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007211:Indoles; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology*; D002722:Chlorobenzenes; D000098826:Bisphenol A Compounds
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide; D001559:Benzhydryl Compounds; D004852:Epoxy Compounds; D005947:Glucose; D007211:Indoles; D007328:Insulin; D047493:PPAR alpha; D047495:PPAR gamma; D011720:Pyrazoles; D011743:Pyrimidines; D012265:Ribonucleotides; C060893:MK-886; D002722:Chlorobenzenes; C516138:dorsomorphin; C031143:AICA ribonucleotide; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds