Hydrogen Sulfide and Glucose Homeostasis: A Tale of Sweet and the Stink.

SIGNIFICANCE: Among many endogenous mediators, the gasotransmitter hydrogen sulfide (H2 S) plays an important role in the regulation of glucose homeostasis. In this article we discuss different functional roles of H2 S in several metabolic organs/tissues required in the maintenance of glucose homeostasis. Recent Advances: New evidence has emerged revealing the insulin sensitizing role of H2 S in adipose tissue and skeletal muscle biology. In addition, H2 S was demonstrated to be a potent stimulator of gluconeogenesis via the induction and stimulation of various glucose-producing pathways in the liver.

CRITICAL ISSUES: Similar to its other physiological effects, H2 S exhibits paradoxical characteristics in the regulation of glucose homeostasis: (1) H2 S stimulates glucose production via activation of gluconeogenesis and glycogenolysis in hepatocytes, yet inhibits lipolysis in adipocytes; (2) H2 S stimulates glucose uptake into adipocytes and skeletal muscle but inhibits glucose uptake into hepatocytes; (3) H2 S inhibits insulin secretion from pancreatic β cells, yet sensitizes insulin signaling and insulin-triggered response in adipose tissues and skeletal muscle. It is also unclear the impact H2 S may have on glucose metabolism and utilization by other vital organs, such as the brain.

FUTURE DIRECTIONS: Recent reports and ongoing studies lay the foundation for a general, although highly incomplete, understanding of the effect of H2 S on regulating glucose homeostasis. In this review, we describe the molecular mechanisms and physiological outcomes of the gasotransmitter H2 S on organs and tissues required for homeostatic maintenance of blood glucose. Future directions highlighting the H2 S-mediated homeostatic control of glucose metabolism under physiological and insulin-resistant conditions are also discussed. Antioxid. Redox Signal. 28, 1463-1482.