Mol Cell Biochem. 2010 Jun 24. [Epub ahead of print]
Activation of PPARdelta promotes mitochondrial energy metabolism and decreases basal insulin secretion in palmitate-treated beta-cells.
Jiang L, Wan J, Ke LQ, Lü QG, Tong NW.
Department of Endocrinology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, Sichuan, 610041, China, email@example.com.
The peroxisome proliferator-activated receptor delta (PPARdelta) 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 PPARdelta in insulin-secreting beta-cells, however, is not well understood; we recently identified the cell-specific role of PPARdelta 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 PPARdelta agonist GW501516, we detected the gene expression changes for transcripts, such as peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1alpha), 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-1alpha, 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 PPARdelta 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.
PMID: 20571903 [PubMed - as supplied by publisher]