Cystathionine gamma-lyase/hydrogen sulfide system and glucose homeostasis

Abstract

Research in the last twenty years has transformed the role of hydrogen sulfide (H2S) being perceived from a toxic gas to a gaso-transmitter with diverse physiological and pathological significance. Cystathionine gamma-lyase (CSE) is the major enzyme responsible for the endogenous production of H2S in pancreatic β cells and liver cells, which are two key types of cells to regulate glucose level. The hallmarks of type 2 diabetes mellitus consist of insulin resistance, pancreatic β-cell dysfunction, and increased endogenous glucose production by liver. Pathophysiological implications of the CSE/H2S system in both type 1 and type 2 diabetes as well as diabetic complications have been reported before. Previous studies in our laboratory have shown that endogenous H2S mainly produced from CSE inhibited insulin release via activating KATP channels and decreased H2S production was observed after exposure to elevated glucose level in pancreatic β cells. However, the effect of glucose on CSE gene expression in pancreatic β cells and the underlying mechanism have not been thoroughly explored. Liver, an important organ to control glucose level, has relatively high amount of H2S production compared to other organs and CSE has been reported to be the major enzyme responsible for it. The aim of the current study was to investigate the effect of glucose on CSE expression in INS-1E cells (insulin-secreting β cells) and the role of H2S on basal and insulin-stimulated glucose uptake, glycogen synthesis and gluconeogenesis in human hepatoma HepG2 cells as well as the underlying mechanisms.