title: Forkhead box class O family member proteins: The biology and pathophysiological roles in diabetes.
abstract: 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.
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kyoichiro
authors.identifier: http://orcid.org/0000-0001-9829-1018
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Japan Agency for Medical Research and Development, CREST, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology; D050356:Lipid Metabolism; D010179:Pancreas / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D015398:Signal Transduction
chemical_list: D051858:Forkhead Transcription Factors; D005947:Glucose
keywords: Diabetes; Forkhead box class O family member proteins; Insulin signaling