Open AccessForkhead box class O family member proteins: The biology and pathophysiological roles in diabetes
Author(s) -
Tsuchiya Kyoichiro,
Ogawa Yoshihiro
Publication year - 2017
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12651
Subject(s) - foxo1 , dyslipidemia , diabetes mellitus , glucose homeostasis , medicine , oxidative stress , lipid metabolism , endocrinology , transcription factor , signal transduction , biology , microbiology and biotechnology , insulin resistance , biochemistry , gene , protein kinase b
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 the 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 the pancreas, FoxO1 is necessary to maintain β‐cell differentiation, and could be promising targets for β‐cell regeneration. In endothelial cells, FoxOs strongly promote atherosclerosis through suppressing nitric oxide production and enhancing inflammatory responses. In the present review, we summarize the basic biology and pathophysiological significance of FoxOs in diabetes.