Forkhead box class O family member proteins: The biology and pathophysiological roles in diabetes.
Kyoichiro TsuchiyaYoshihiro OgawaPublished in: Journal of diabetes investigation (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 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.
Keyphrases
- transcription factor
- cell cycle
- type diabetes
- cardiovascular disease
- blood glucose
- glycemic control
- nitric oxide
- dna binding
- endothelial cells
- cell proliferation
- signaling pathway
- stem cells
- fatty acid
- poor prognosis
- genome wide identification
- single cell
- binding protein
- risk factors
- cell death
- endoplasmic reticulum stress
- bone marrow
- physical activity
- body mass index
- skeletal muscle