Peroxisome Proliferator-Activated Receptor (PPAR ) Potentiates, whereas PPAR Attenuates, Glucose- Stimulated Insulin Secretion in Pancreatic -Cells

摘要: Fatty acids (FAs) are known to be important regulators of insulin secretion from pancreatic -cells. FA-coenzyme A esters have been shown directly stimulate the process, whereas long-term exposure -cells FAs compromises glucose-stimulated (GSIS) by mechanisms unknown date. It has speculated that some these effects mediated members peroxisome proliferator-activated receptor (PPAR) family via an induction uncoupling protein-2 (UCP2). In this study we show adenoviral coexpression PPAR and retinoid X (RXR ) in INS-1E synergistically a doseand ligand-dependent manner increases expression target genes enhances FA uptake -oxidation. contrast, ectopic /RXR deposition as triacylglycerides. Although leads UCP2 mRNA protein, is not accompanied reduced hyperpolarization mitochondrial membrane, indicating under conditions, increased insufficient for dissipation proton gradient. Importantly, attenuates GSIS, potentiates GSIS rat islets cells without affecting membrane potential. These results strong subtype specificity two subtypes on lipid partitioning when systematically compared -cell context. (Endocrinology 146: 3266–3276, 2005)