Regulation of carbohydrate metabolism by nitric oxide and hydrogen sulfide: Implications in diabetes

Nitric oxide (NO) and hydrogen sulfide (H₂S) are two gasotransmitters that are produced in the human body and have a key role in many of the physiological activities of the various organ systems. Decreased NO bioavailability and deficiency of H₂S are involved in the pathophysiology of type 2 diabetes and its complications. Restoration of NO levels have favorable metabolic effects in diabetes. The role of H₂S in pathophysiology of diabetes is however controversial; H₂S production is decreased during development of obesity, diabetes, and its complications, suggesting the potential therapeutic effects of H₂S. On the other hand, increased H₂S levels disturb the pancreatic β-cell function and decrease insulin secretion. In addition, there appear to be important interactions between NO and H₂S at the levels of both biosynthesis and signaling pathways, yet clear an insight into this relationship is lacking. H₂S potentiates the effects of NO in the cardiovascular system as well as NO release from its storage pools. Likewise, NO increases the activity and the expression of H₂S-generating enzymes. Inhibition of NO production leads to elimination/attenuation of the cardioprotective effects of H₂S. Regarding the increasing interest in the therapeutic applications of NO or H₂S-releasing molecules in a variety of diseases, particularly in the cardiovascular disorders, much is to be learned about their function in glucose/insulin metabolism, especially in diabetes. The aim of this review is to provide a better understanding of the individual and the interactive roles of NO and H₂S in carbohydrate metabolism.