Tsuchiya K, Ogawa Y, et al.
Department of Diabetes, Endocrinology and Metabolism, Medical Hospital of Tokyo Medical and Dental University.
Journal of diabetes investigation. Mar 2017.
Forkhead box class O family member proteins (FoxOs) of transcription factors are essential regulators of cellular homeostasis, including glucose and lipid metabolism, oxidative stress response and redox signaling, cell cycle progression and apoptosis. Altered FoxO1 expression and activity have been associated with glucose intolerance, dyslipidemia, and complications of diabetes. In liver, they direct carbons to glucose or lipid utilization, thus providing a unifying mechanism for the two abnormalities of the diabetic liver: excessive glucose production, and increased lipid synthesis and secretion. In pancreas, FoxO1 is necessary to maintain beta cell differentiation, and could be promising targets for β-cell regeneration. In endothelial cells, FoxOs strongly promote atherosclerosis via suppressing nitric oxide production and enhancing inflammatory responses. In this review, we summarize the basic biology and pathophysiological significance of FoxOs in diabetes. This article is protected by copyright. All rights reserved.