Implications of Hydrogen Sulfide in Glucose Regulation: How H(2)S Can Alter Glucose Homeostasis through Metabolic Hormones

Diabetes and its comorbidities continue to be a major health problem worldwide. Understanding the precise mechanisms that control glucose homeostasis and their dysregulation during diabetes are a major research focus. Hydrogen sulfide (H(2)S) has emerged as an important regulator of glucose homeostasis. This is achieved through its production and action in several metabolic and hormone producing organs including the pancreas, liver, and adipose. Of importance, H(2)S production and signaling in these tissues are altered during both type 1 and type 2 diabetes mellitus. This review first examines how H(2)S is produced both endogenously and by gastrointestinal microbes, with a particular focus on the altered production that occurs during obesity and diabetes. Next, the action of H(2)S on the metabolic organs with key roles in glucose homeostasis, with a particular focus on insulin, is described. Recent work has also suggested that the effects of H(2)S on glucose homeostasis goes beyond its role in insulin secretion. Several studies have demonstrated important roles for H(2)S in hepatic glucose output and adipose glucose uptake. The mechanism of H(2)S action on these metabolic organs is described. In the final part of this review, future directions examining the roles of H(2)S in other metabolic and glucoregulatory hormone secreting tissues are proposed.