The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse
Open accessAbstract
Insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute to the development of these disorders, the molecular mechanism is poorly understood. Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c. Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia. In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity. Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.
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Cites
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Nonalcoholic Fatty Liver Disease
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Self-citationSOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2
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Self-citationSREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology
Shimano, H., & Sato, R. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.91 · Cited by 1,174
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Self-citationPositive and negative regulation of insulin signaling through IRS-1 phosphorylation
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Arsenic and human health effects: A review
Mohammed Abdul, K. S., Jayasinghe, S. S., Chandana, E. P. S., Jayasumana, C., & De Silva, P. M. C. S. (2015) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2015.09.016 · Cited by 907
Metadata
- Authors
- Ueki, K., Kondo, T., Tseng, Y.-H., & Kahn, C. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-07-06
- Volume
- 101
- Issue
- 28
- Pages
- 10422-10427
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1998002161
- Cited by
- 384
- References
- 12
- FWCI
- 17.78
- Type
- journal article
- Language
- en
- Open access
- green
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- Ueki, K., Kondo, T., Tseng, Y.-H., & Kahn, C. R. (2004). Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0402511101
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