Role of Lipid Peroxidation and PPAR-δ in Amplifying Glucose-Stimulated Insulin Secretion

• DOI: 10.2337/db11-0347
• Publication Date: 2011-09-07T04:16:26Z
• Authors: Guy Cohen; Yael Riahi; Ofer Shamni; Michel Guichardant; Chryssostomos Cha...; Carla Ferreri; Nurit Kaiser; Shlomo Sasson
• Keywords: Male; Cell Line; Islets of Langerhans; 03 medical and health sciences; Insulin-Secreting Cells; Insulin Secretion; Animals; Humans; Insulin; Gene Silencing; PPAR delta; Rats, Wistar; Aldehydes; 0303 health sciences; diabetes; Group IV Phospholipases A2; Rats; Islet Studies; Diabetes Mellitus, Type 2; Hyperglycemia; Fatty Acids, Unsaturated; lipidomics; membrane remodeling; Lipid Peroxidation; Gerbillinae; Reactive Oxygen Species

Previous studies show that polyunsaturated fatty acids (PUFAs) increase the insulin secretory capacity of pancreatic β-cells. We aimed at identifying PUFA-derived mediators and their cellular targets are involved in amplification release from β-cells preexposed to high glucose levels.The content phospholipids INS-1E was determined by lipidomics analysis. High-performance liquid chromatography used identify peroxidation products β-cell cultures. Static dynamic glucose-stimulated secretion (GSIS) assays were performed on isolated rat islets and/or cells. The function peroxisome proliferator-activated receptor-δ (PPAR-δ) regulating investigated using pharmacological agents gene expression manipulations.High activated cPLA(2) and, subsequently, hydrolysis arachidonic linoleic acid (AA LA, respectively) Glucose also increased level reactive oxygen species, which promoted these PUFAs generate 4-hydroxy-2E-nonenal (4-HNE). latter mimicked GSIS-amplifying effect preexposure PPAR-δ agonist GW501516 cells islets. These effects blocked with GSK0660, a selective antagonist, antioxidant N-acetylcysteine or silencing expression. High glucose, 4-HNE, induced luciferase PPAR-δ-mediated transactivation assay. Cytotoxic 4-HNE observed only above physiologically effective concentration range.Elevated levels augment AA LA This molecule is an endogenous ligand for PPAR-δ, amplifies