Chronic palmitate exposure inhibits AMPKα and decreases glucose‐stimulated insulin secretion from β‐cells: modulation by fenofibrate 1

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 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.