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Mol Cell Biochem. 2010 Oct;343(1-2):249-56. doi: 10.1007/s11010-010-0520-8. Epub 2010 Jun 24.

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

Author information

1
Department of Endocrinology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. jiang_li71@163.com

Abstract

The peroxisome proliferator-activated receptor δ (PPARδ) 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 PPARδ in insulin-secreting β-cells, however, is not well understood; we recently identified the cell-specific role of PPARδ on mitochondrial energy metabolism and insulin secretion in lipotoxic β-cells. After treatment of HIT-T15 cells, a syrian hamster pancreatic β-cell line, with high concentrations of palmitate and/or the specific PPARδ agonist GW501516, we detected the gene expression changes for transcripts, such as peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1α), 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-1α, 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 β-cells. GW501516-induced activation of PPARδ 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 β-cells.

PMID:
20571903
DOI:
10.1007/s11010-010-0520-8
[Indexed for MEDLINE]

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