The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
FoxO integration of insulin signaling with glucose and lipid metabolism
Open accessAbstract
The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA-binding domain, known as ‘forkhead box’ domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senescence, autophagy and aging. Genetic mutations in FoxO genes or abnormal expression of FoxO proteins are associated with metabolic disease, cancer or altered lifespan in humans and animals. Of the FoxO family, FoxO6 is the least characterized member and is shown to play pivotal roles in the liver, skeletal muscle and brain. Altered FoxO6 expression is associated with the pathogenesis of insulin resistance, dietary obesity and type 2 diabetes and risk of neurodegeneration disease. FoxO6 is evolutionally divergent from other FoxO isoforms. FoxO6 mediates insulin action on target genes in a mechanism that is fundamentally different from other FoxO members. Here, we focus our review on the role of FoxO6, in contrast with other FoxO isoforms, in health and disease. We review the distinctive mechanism by which FoxO6 integrates insulin signaling to hepatic glucose and lipid metabolism. We highlight the importance of FoxO6 dysregulation in the dual pathogenesis of fasting hyperglycemia and hyperlipidemia in diabetes. We review the role of FoxO6 in memory consolidation and its contribution to neurodegeneration disease and aging. We discuss the potential therapeutic option of pharmacological FoxO6 inhibition for improving glucose and lipid metabolism in diabetes.
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Cites
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Cited by
The regulation of FOXO1 and its role in disease progression
Xing, Y.-Q., Li, A., Yang, Y., Li, X.-X., Zhang, L.-N., & Guo, H.-C. (2018) · Life Sciences · doi:10.1016/j.lfs.2017.11.030 · Cited by 420
Genetic and epigenetic regulation of human aging and longevity
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Proteomics in aging research: A roadmap to clinical, translational research
Moaddel, R., Ubaida‐Mohien, C., Tanaka, T., Lyashkov, A., Basisty, N., Schilling, B., Semba, R. D., Franceschi, C., Gorospe, M., & Ferrucci, L. (2021) · Aging Cell · doi:10.1111/acel.13325 · Cited by 139
ApoE4 attenuates autophagy via FoxO3a repression in the brain
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Metadata
- Authors
- Lee, S., & Dong, H. H.
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2017-05
- Volume
- 233
- Issue
- 2
- Pages
- R67-R79
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2588176311
- Cited by
- 360
- References
- 13
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- bronze
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