Dongyun Shi
Fudan University, China
Title: MitoPBN prevents reactive oxygen species-mediated mitochondria abnormalities and metabolic reprogram in diabetic mice
Biography
Biography: Dongyun Shi
Abstract
Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in the diabetes process, however the underlying mechanisms are still unclear. Our previous results has shown ROS-mediated glucose metabolic reprogram induces insulin resistance in type 2 diabetes. In this study, we using MitoPBN, a mitochondrial targeted free radical scavenger, study the role of mitochondrial-derived ROS in the occurrence of diabetes. By using STZ-induced type 2 diabetic mice, we found that the diabetic mice showed an increased oxidative stress level in parallel with the raised blood glucose and impaired glucose tolerance. Meanwhile, the mitochondria-related protein, such as SIRT3, mitochondria fusion protein MFN-1 and 2, was dysregulated, thus contributing to the impaired respiratory ability and declined adenylate energy charge. In concordance with the mitochondria dysfunction, the glucose metabolism was disordered. MitoPBN treatment reduced NADH:NAD+ ratio, activated the SIRT, PCG-1α and phospho-AMPK, enhanced respiratory ability and increased adenylate energy charge so that alleviated ROS induced-mitochondria dysfunction. MitoPBN also increased glycolysis while decreased gluoconeogenisis, reversing the ROS induced-metabolic reprogram in diabetic mice. Our study suggests mitochondria-derived ROS play an important role in occurrence of diabetes. MitoPBN could be a potential drug to treat diabetes by improving mitochondrial bioenegetis ability and preventing ROS induced metabolic disorder