Roles of Hydrogen Sulfide in the Pathogenesis of Diabetes Mellitus and Its Complications

SIGNIFICANCE: Diabetes and its complications represent a major socioeconomic problem. RECENT ADVANCES: Changes in the balance of hydrogen sulfide (H(2)S) play an important role in the pathogenesis of β-cell dysfunction that occurs in response to type 1 and type 2 diabetes. In addition, changes in H(2)S homeostasis also play a role in the pathogenesis of endothelial injury, which develop on the basis of chronically or intermittently elevated circulating glucose levels in diabetes. CRITICAL ISSUES: In the first part of this review, experimental evidence is summarized implicating H(2)S overproduction as a causative factor in the pathogenesis of β-cell death in diabetes. In the second part of our review, experimental evidence is presented supporting the role of H(2)S deficiency (as a result of increased H(2)S consumption by hyperglycemic cells) in the pathogenesis of diabetic endothelial dysfunction, diabetic nephropathy, and cardiomyopathy. FUTURE DIRECTIONS: In the final section of the review, future research directions and potential experimental therapeutic approaches around the pharmacological modulation of H(2)S homeostasis in diabetes are discussed.