线粒体与2型糖尿病.ppt

1) 线粒体上表达的蛋白的功能对线粒体功能的影响及对肝细胞功能的影响。 2) 原本不在线粒体上表达的蛋白，但在线粒体上形成蛋白功能复合物，进而影响线粒体功能和肝细胞功能。 3) 原本不在线粒体上表达，但通过调节相关基因如NRF1等从而调控线粒体数量和功能的蛋白。 4) 线粒体蛋白组学的研究。 Cloning of UCP Homologues Amino Acid Sequence Identity to UCP1 UCP2 is Upregulated in Pancreatic Islets of ob/ob Mice Superoxide is a Normal Byproduct of Mitochondrial Electron Transport Chain Activity Superoxide is created when O2 reacts with radicals in the electron transport chain Acknowledgements Obesity Hyperglycemia ? UCP2 Protein ? Superoxide ? UCP2 Activity ?-Cell Dysfunction Insulin Secretion (% of Insulin Content) Chronic Hyperglycemia (25 mM) and ?-Cell Dysfunction 0 2 4 6 Chronic 5.5 mM Chronic 25 mM Chronic 25 mM + MnSOD Chronic 25 mM + GPX1 * * * * # # # 5.5 mM 12.5 mM 25 mM Insulin Secretion (% of Insulin Content) Chronic Hyperglycemia (25 mM) and ?-Cell Dysfunction 0 2 4 6 Chronic 5.5 mM Chronic 25 mM Chronic 25 mM + MnSOD Chronic 25 mM + GPX1 * * * * # # # 5.5 mM 12.5 mM 25 mM Effect of removing O2? (+SOD) Insulin Secretion (% of Insulin Content) Chronic Hyperglycemia (25 mM) and ?-Cell Dysfunction 0 2 4 6 Chronic 5.5 mM Chronic 25 mM Chronic 25 mM + MnSOD * * * * # # 5.5 mM 12.5 mM 25 mM Effect of UCP2 Knockout # * Chronic 25 mM * ob/ob ob/ob + SOD ob/ob + UCP2 KO 0 2 4 6 Insulin Secretion (% of Insulin Content) Obesity and ?-Cell Dysfunction (ob/ob Islets) ob/ob ob/ob + SOD ob/ob + UCP2 KO 0 2 4 6 Insulin Secretion (% of Insulin Content) Obesity and ?-Cell Dysfunction (ob/ob Islets) Effect of removing O2? (+SOD) ob/ob ob/ob + SOD ob/ob + UCP2 KO 0 2 4 6 Insulin Secretion (% of Insulin Content) Obesity and ?-Cell Dysfunction (ob/ob Islets) Effect of UCP2 Knockout Zhang CY et al, J. CLIN. INVEST. 112 (12): 1831-1842 2003 UCP2 is a negative regulator of insulin secretion. Endogenous superoxide actives UCPs. Interrupting the pathway of superoxide-mediated activation of UCP2 in islets prevents the loss of GSIS that normally results from chronic hyperglycemia, or obesity. Inhibition of