Sirtuins as therapeutic targets in diabetes.

Sirtuins (SIRTs) are NAD+-dependent deacetylases that mediate post-translational modifications of proteins. Seven members of the SIRT family have been identified in mammals. Importantly, SIRTs interact with numerous metabolic and inflammatory pathways. Thus, researchers have investigated their role in metabolic and inflammatory disorders. In this review, we comprehensively discuss the involvement of SIRTs in the processes of pancreatic β-cell dysfunction, glucose tolerance, insulin secretion, lipid metabolism, and adipocyte functions. In addition, we describe the current evidence regarding modulation of the expression and activity of SIRTs in diabetes, diabetic complications, and obesity. The development of specific SIRT activators and inhibitors that exhibit high selectivity toward specific SIRT isoforms remains a major challenge. This involves the need to elucidate the physiological pathways involving SIRTs, as well as their important role in the development of metabolic disorders. Molecular modeling techniques will be helpful to develop new compounds that modulate the activity of SIRTs, which may contribute to the preparation of new drugs that selectively target specific SIRTs. SIRTs hold promise as potential targets in metabolic disease, but there is much to learn about specific modulators and the final answers will await clinical trials.