Activation of PPAR delta up-regulates the expression of insulin gene transcription factor MafA and ameliorates glucose-induced insulin secretion impaired by palmitate

作者：Cao Mingming; Long Yang; Tong Yuzhen; Wan Jun; Tong Nanwei^*

来源：Molecular and Cellular Biochemistry, 2012, 366(1-2): 183-189.

DOI：10.1007/s11010-012-1296-9

• PPAR delta
• MafA
• JNK
• Insulin secretion

PPAR delta, a member of the peroxisome proliferator-activated receptor superfamily, plays a key role in the transcriptional regulation of genes involved in cellular lipid and energy metabolism. Therefore, PPAR delta may represent a new target for the treatment of obesity, hyperlipidemia, and type 2 diabetes. MafA is a beta-cell-specific and glucose-regulated transcriptional activator for insulin gene expression and plays a crucial role in pancreas development, beta-cell differentiation as well as maintenance of beta-cell function. However, little is known about how PPAR delta regulates MafA and ameliorates glucose-stimulated insulin secretion impaired by free fatty acids (FFA). In the present study, we evaluated the basal insulin secretion (BIS), glucose-stimulated insulin secretion (GSIS), and insulin secretion index (ISI) of INS-1E cells that were cultured in media supplemented with or without 0.5 mM palmitate and treated with or without a PPAR delta agonist (GW501516) or PPAR delta siRNA. The expression of MafA, glucose transportor-2 (GLUT2), and insulin was found to be up-regulated in cells treated with GW501516. Finally, analysis of the level of JNK phosphorylation revealed that activated PPAR delta could inhibit the activation of JNK and increase the expression of MafA. Accordingly, the insulin secretion dysfunction in lipotoxic INS-1E cells was improved. Collectively, these results demonstrate that activation of PPAR delta improves insulin secretion impaired by palmitate and plays a role in the JNK-MafA-GLUT2 pathway.

• 出版日期2012-7
• 单位四川大学