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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.