Activation of PPARδ promotes mitochondrial energy metabolism and decreases basal insulin secretion in palmitate-treated β-cells

作者：Jiang, Li; Wan, Jun; Ke, Lin-qiu; Lue, Qing-guo; Tong, Nan-wei^*

来源：Molecular and Cellular Biochemistry, 2010, 343(1-2): 249-256.

DOI：10.1007/s11010-010-0520-8

• PPAR delta
• beta-cell
• Mitochondria
• Insulin secretion
• Energy metabolism

The peroxisome proliferator-activated receptor delta (PPAR delta) regulates the expression of genes involved in cellular lipid and cell energy metabolism in many metabolically active tissues, such as liver, muscle, and fat, and plays a role in the cellular response to stress and environmental stimuli. The particular role of PPAR delta in insulin-secreting beta-cells, however, is not well understood; we recently identified the cell-specific role of PPAR delta on mitochondrial energy metabolism and insulin secretion in lipotoxic beta-cells. After treatment of HIT-T15 cells, a syrian hamster pancreatic beta-cell line, with high concentrations of palmitate and/or the specific PPAR delta agonist GW501516, we detected the gene expression changes for transcripts, such as peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1 alpha), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (mtTFA), the protein levels of the mitochondria uncoupling protein 2 (UCP2), mitochondrial morphology, the insulin secretion capacity and ATP/ADP ratio. Our results show that GW501516 treatment promoted generation of mitochondrial ATP, as well as expression levels of PGC-1 alpha, NRF-1 and mtTFA, decreased basal insulin secretion, but had no effect on glucose-stimulated insulin secretion (GSIS), increased amounts of UCP2 and changed ATP-to-ADP ratio, improved mitochondrial morphology in palmitate-treated beta-cells. GW501516-induced activation of PPAR delta enhanced mitochondrial energy metabolism, but also promoted a concomitant mitochondrial uncoupling and resulted in decreased basal insulin secretion and restricted GSIS; this observation indicated the possible action of a protective mechanism responding to the alleviation of excessive lipid load and basal insulin secretion in lipotoxic beta-cells.

• 出版日期2010-10
• 单位四川大学