Significance: Diabetes and its complications represent a major socioeconomic problem. Recent Advances: Changes in the balance of hydrogen sulfide (H2S) 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 H2S 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 H2S 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 H2S deficiency (as a result of increased H2S 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 H2S homeostasis in diabetes are discussed. Antioxid. Redox Signal. 17, 68–80.
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