Details

Autor(en) / Beteiligte

• Ying SUN Meng REN Guan-qi GAO Bendi GONG Wei XIN Hua GUO Xiu-juan ZHANG Ling GAO Jia-jun ZHAO

Titel

Chronic palmitate exposure inhibits AMPKa and decreases glucose-stimulated insulin secretion from β-cells： modulation by fenofibrate

Ist Teil von

• Acta pharmacologica Sinica, 2008, Vol.29 (4), p.443-450

Erscheinungsjahr

2008

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 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 β-cells to palmitate for 48 h inhibited the expression of AMPKαO 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 el- evation 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.