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

• Published in: Molecular and cellular biochemistry Vol. 343; no. 1-2; pp. 249 - 256
• Main Authors: Jiang, Li, Wan, Jun, Ke, Lin-qiu, Lü, Qing-guo, Tong, Nan-wei
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.10.2010; Springer US
• Subjects: Animals; Base Sequence; Biochemistry; Biomedical and Life Sciences; Cardiology; Cell Line; Chromatography, High Pressure Liquid; DNA Primers; Energy Metabolism; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Life Sciences; Medical Biochemistry; Microscopy, Electron, Transmission; mitochondria; Mitochondria - metabolism; Oncology; Palmitic Acid - pharmacology; Polymerase Chain Reaction; PPAR delta - metabolism; PPARδ; β-cell; Mitochondria; Energy metabolism; β-cell; PPARδ; Insulin secretion
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-010-0520-8

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.