236 - Hydrogen Sulfide Increases GSH Biosynthesis, Glucose Uptake and Utilization in Mouse Myotubes

Abstract

Diabetes is a leading cause of chronic diseases, such as heart disease. Diabetic patients have lower blood concentrations of H 2 S and L-Cysteine (LC). LC undergoes enzymatic breakdown to produce hydrogen sulphide (H 2 S), a gasotransmitter that regulates glucose and lipid homeostasis. Using C2C12 mouse myoblast (differentiated into myotubes) as a model, this study investigates the hypothesis that beneficial effects of LC supplementation are mediated by the upregulation of H 2 S status in diabetic patients. Results show that exogenous administration of Sodium hydrosulfide (NaHS 10µM; 6 hours), a H 2 S donor, significantly ( p 2 S production induced by using CSE siRNA caused an increase in ROS, and down regulation of potent antioxidant GSH biosynthesis enzymes (GCLC, Glutathione Synthetase) but not GGLM. Further, CSE knockdown downregulate Glucose Transporter Type 4 (GLUT4) mRNA level and reduces glucose uptake in C2C12 myotubes. Taken together, these data suggest that the upregulation of physiological levels of H 2 S can have beneficial effects on glucose homeostasis and redox balance via GSH pathway. Further mechanistic studies are under investigation on how H 2 S regulate GSH biosynthesis and L-Cysteine transporter (SLC7A11) in the maintenance of glucose homeostasis. Supported by NIH/NCCIH RO1 AT007442