H2O2-Activated Mitochondrial Phospholipase iPLA2 gamma Prevents Lipotoxic Oxidative Stress in Synergy with UCP2, Amplifies Signaling via G-Protein-Coupled Receptor GPR40, and Regulates Insulin Secretion in Pancreatic beta-Cells

0451864 - FGÚ 2016 RIV US eng J - Journal Article
Ježek, Jan - Dlasková, Andrea - Zelenka, Jaroslav - Jabůrek, Martin - Ježek, Petr
H2O2-Activated Mitochondrial Phospholipase iPLA2 gamma Prevents Lipotoxic Oxidative Stress in Synergy with UCP2, Amplifies Signaling via G-Protein-Coupled Receptor GPR40, and Regulates Insulin Secretion in Pancreatic beta-Cells.
Antioxidants & Redox Signaling. Roč. 23, č. 12 (2015), s. 958-972. ISSN 1523-0864. E-ISSN 1557-7716
R&D Projects: GA ČR(CZ) GPP303/11/P320; GA ČR(CZ) GA13-02033S; GA ČR(CZ) GA13-06666S; GA ČR GA15-02051S
Institutional support: RVO:67985823
Keywords : mitochondrial phospholipase iPLA2 gamma * uncoupling protein UCP2 * G-protein coupled receptor - 40 * glucose-stimulated insulin secretion * pancreatic beta cells
Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition
Impact factor: 7.093, year: 2015

When directly stimulated by hydrogen peroxide, the mitochondrial phospholipase iPLA2 gamma cleaves fatty acids to initiate uncoupling mediated by UCP2, which then attenuates mitochondrial superoxide formation. The synergy of iPLA2 gamma and UCP2 thus leads to cytoprotection. Moreover, fatty acid beta oxidation initiates iPLA2 gamma cleavage of mitochondrial fatty acids which spread up to the plasma membrane and activate G-protein coupled receptor-40 (GPR40) that subsequently initiates insulin secretion by so-called glycerolipid/fatty acid cycle
Permanent Link: http://hdl.handle.net/11104/0252926