SIRT1-FOXOs activity regulates diabetic complications

The prevalence of diabetes is continuously increasing in the recent decades. Persistent hyperglycemia, hyperinsulinemia and the subsequent oxidative stress result in diabetic complications, primarily categorized as microvascular (nephropathy, retinopathy and neuropathy) and macrovascular (cardiomyopathy) complications. The complications are prevalent in both type 1 and type 2 diabetic patients. Polyol pathway, elevated AGE production, PKC activation and hexosamine pathway are indeed the critical pathways involved in the progression of diabetic complications. Silent information regulator 2 or SIR2 or more commonly known as sirtuins are NAD+ dependent histone deacetylase. SIRT1, a member of the sirtuin family has been extensively studied for its role in lifespan extension and needs to be explored for its beneficial effects in diabetic complications. Moreover, it is also known to regulate the activity of other proteins and transcription factors. One such substrate of SIRT1 is FOXOs transcription factor which has gained much attention as the mediator of various cellular processes such as cell cycle arrest and proliferation, DNA repair and metabolism. It has been reported that SIRT1 regulates the activity of FOXOs, whereas few recent advances also suggest a role FOXOs in governing the activity of SIRT1, which permits for a crosstalk between SIRT1 and FOXOs. Therefore, the focus of the present review is to describe and explore the interaction between SIRT1 and FOXOs, predominantly FOXO1 and FOXO3 and to understand the underlying mechanism of SIRT1-FOXOs in controlling and alleviating diabetic complications. Thus, this crosstalk suggests that SIRT1 and FOXOs may serve as potential therapeutic targets in treating diabetic complications.