Abstract
Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS) and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response.
Highlights
Diabetes mellitus is a chronic disease characterized by elevated blood sugar levels resulting from either lack of insulin production or resistance to insulin
Accumulating evidence suggests that hyperglycemia-induced production of free radicals and the subsequent oxidative stress contributes to the development and progression of diabetes and related complications [6,7,8]
Experimental Diabetes Research cell types, Reactive oxygen species (ROS) lead to the activation of the forkhead box O (FOXO) transcription factors that include FOXO1, FOXO3, and FOXO4, which can mediate the effects of ROS through regulation of gene transcription
Summary
Diabetes mellitus is a chronic disease characterized by elevated blood sugar levels resulting from either lack of insulin production or resistance to insulin. Reactive oxygen species (ROS) are oxygen free radicals that are generated as by-products of mitochondrial metabolism and function as signaling molecules in various intracellular processes including cell proliferation, migration, and apoptosis [9]. Experimental Diabetes Research cell types, ROS lead to the activation of the forkhead box O (FOXO) transcription factors that include FOXO1, FOXO3, and FOXO4, which can mediate the effects of ROS through regulation of gene transcription. These transcription factors have been implicated in diverse cellular processes ranging from glucose metabolism to cell behavior including cell cycle and apoptosis [16, 17]. We will use the term FOXO for all or any of the FOXO transcription factors throughout this paper, unless otherwise specified
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