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

Abstract 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.