The Role of Forkhead Box O in Pathogenesis and Therapy of Diabetes Mellitus

Abstract

Type 2 diabetes is a disease that causes numerous complications disrupting the functioning of the entire body. Therefore, new treatments for the disease are being sought. Studies in recent years have shown that forkhead box O (FOXO) proteins may be a promising target for diabetes therapy. FOXO proteins are transcription factors involved in numerous physiological processes and in various pathological conditions, including cardiovascular diseases and diabetes. Their roles include regulating the cell cycle, DNA repair, influencing apoptosis, glucose metabolism, autophagy processes and ageing. FOXO1 is an important regulator of pancreatic beta-cell function affecting pancreatic beta cells under conditions of insulin resistance. FOXO1 also protects beta cells from damage resulting from oxidative stress associated with glucose and lipid overload. FOXO has been shown to affect a number of processes involved in the development of diabetes and its complications. FOXO regulates pancreatic β-cell function during metabolic stress and also plays an important role in regulating wound healing. Therefore, the pharmacological regulation of FOXO proteins is a promising approach to developing treatments for many diseases, including diabetes mellitus. In this review, we describe the role of FOXO proteins in the pathogenesis of diabetes and the role of the modulation of FOXO function in the therapy of this disease.