@article{APS6307,
author = {Ying Sun and Meng Ren and Guan-qi Gao and Bendi Gong and Wei Xin and Hua Guo and Xiu-juan Zhang and Ling Gao and Jia-jun Zhao},
title = {Chronic palmitate exposure inhibits AMPKα and decreases glucose-stimulated insulin secretion from β-cells: modulation by fenofibrate},
journal = {Acta Pharmacologica Sinica},
volume = {29},
number = {4},
year = {2016},
keywords = {},
abstract = {Aim: Adenosine monophosphate-activated protein kinase (AMPK), a vital regulator of glucose metabolism, may affect insulin secretion in β-cells. However, the role of AMPK in β-cell lipotoxicity remains unclear. Fenofibrate has been reported to regulate lipid homeostasis and is involved in insulin secretion in pancreatic β-cells. In the present study, we aimed to investigate the effect of palmitate on AMPK expression and glucose-stimulated insulin secretion (GSIS) in rat islets and INS-1 β-cell, as well as the effect of fenofibrate on AMPK and GSIS in INS-1 cells treated with palmitate.
Methods: Isolated rat islets and INS-1 β-cells were treated with and without palmitate or fenofibrate for 48 h. The mRNA levels of the AMPKαisoforms were measured by real-time PCR. Western blotting was used to detect the protein expression of total AMPKα (T-AMPKα), phosphorylated AMPKα (P-AMPKα), and phosphorylated acetyl coenzyme A carboxylase (P-ACC). Insulin secretion was detected by radioimmunoassay induced by 20 mmol/L glucose as GSIS.
Results: The results showed that chronic exposure of β-cells to palmitate for 48 h inhibited the expression of AMPKα1 mRNA and T-AMPKα protein levels, as well as P-AMPKα and P-ACC protein expressions in a dose-dependent manner. Accordingly, GSIS was inhibited by palmitate. Compared with the palmitate-treated cells, fenofibrate ameliorated these changes impaired by palmitate and exhibited a significant elevation in the expression of AMPKα and GSIS.
Conclusion: Our findings suggest a role of AMPKα reduction in β-cell lipotoxicity and a novel role of fenofibrate in improving GSIS associated with the AMPKα activation in β-cells chronically exposed to palmitate.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6307}
}