Chronic palmitate exposure inhibits AMPKα and decreases glucose-stimulated insulin secretion from -cells: modulation by fenofibrate
Aim: Adenosine monophosphate-activated protein kinase (AMPK), a vital regulator of glucose metabolism, may affect insulin secretion in -cells. However, the role of AMPK in -cell lipotoxicity remains unclear. Fenofibrate has been reported to regulate lipid homeostasis and is involved in insulin secretion in pancreatic -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 -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 -cells were treated with and without palmitate or fenofibrate for 48 h. The mRNA levels of the AMPKα isoforms 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 -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 -cell lipotoxicity and a novel role of fenofibrate in improving GSIS associated with the AMPKα activation in -cells chronically exposed to palmitate.
Document Type: Research Article
Affiliations: 1: Department of Endocrinology, Linyi People's Hospital, Linyi 276003, China 2: Department of Neurology, Case Western Reserve University, Cleveland, OH 44106, USA 3: Central Laboratory of Shandong Provincial Hospital, Shandong University, Jinan 250021, China 4: Department of Endocrinology, Shandong University, Jinan 250021, China
Publication date: 2008-04-01