Emerging links between FOXOs and diabetic complications

Diabetes and its complications are increasing worldwide in the working population as well as in elders. Prolonged hyperglycemia results in damage to blood vessels of various tissues followed by organ damage. Hyperglycemia-induced damage in small blood vessels as in nephrons, retina, and neurons results in diabetic microvascular complications which involve nephropathy, retinopathy, and diabetic neuropathy. Additionally, damage in large blood vessels is considered as a macrovascular complication including diabetic cardiomyopathy. These long-term complications can result in organ failure and thus becomes the leading cause of diabetic-related mortality in patients. Members of the Forkhead Box O family (FOXO) are involved in various body functions including cell proliferation, metabolic processes, differentiation, autophagy, and apoptosis. Moreover, increasing shreds of evidence suggest the involvement of FOXO family members FOXO1, FOXO3, FOXO4, and FOXO6 in several chronic diseases including diabetes and diabetic complications. Hence, this review focuses on the role of FOXO transcription factors in the regulation of diabetic complications.