The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase
Open accessAbstract
Insulin activates sterol regulatory element-binding protein-1c (SREBP-1c) in liver, thereby increasing fatty acid and triglyceride synthesis. We created a line of transgenic rats that produce epitope-tagged human SREBP-1c in liver under control of the constitutive apolipoprotein E promoter/enhancer. This system allows us to dissect the pathway by which insulin stimulates SREBP-1c processing without interference by the insulin-mediated increase in SREBP-1c mRNA. Rats are used because freshly isolated rat hepatocytes respond much more robustly to insulin than do mouse hepatocytes. The data reveal that insulin-mediated stimulation of SREBP-1c processing requires the mechanistic target of rapamycin complex 1 (mTORC1), which also is required for insulin-mediated SREBP-1c mRNA induction. However, in contrast to mRNA induction, insulin stimulation of SREBP-1c processing is blocked by an inhibitor of p70 S6-kinase. The data indicate that the pathways for insulin enhancement of SREBP-1c mRNA and proteolytic processing diverge after mTORC1. Stimulation of processing requires the mTORC1 target p70 S6-kinase, whereas induction of mRNA bypasses this enzyme. Insulin stimulation of both processes is blocked by glucagon. The transgenic rat system will be useful in further defining the molecular mechanism for insulin stimulation of lipid synthesis in liver in normal and diabetic states.
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Self-citationSREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
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Protein Sensors for Membrane Sterols
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Self-citationSREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis
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- 10.1016/S1097-2765(05)00010-9 · doi:10.1016/s1097-2765(05)00010-9 · Paper page
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Mechanisms of Insulin Action and Insulin Resistance
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Huang, X., Liu, G., Guo, J., & Su, Z. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.27173 · Cited by 1,673
“In the feeding state, SREBP-1c is regulated by four pathways: activated AKT stimulates liver X receptor (LXR), which is require for SREBP-1c transcription [64]; activated AKT stimulates mTORC1 to activate SREBP-1c transcription, and mTORC1 also inhibits Lipin-1, which decreases the half-life of nuclear SREBP-1c [65, 6…”
BackgroundSREBP-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
mTOR signalling and cellular metabolism are mutual determinants in cancer
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Metadata
- Authors
- Owen, J. L., Zhang, Y., Bae, S.-H., Farooqi, M. S., Liang, G., Hammer, R. E., Goldstein, J. L., & Brown, M. S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2012-08-27
- Volume
- 109
- Issue
- 40
- Pages
- 16184-16189
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1994173047
- Cited by
- 291
- References
- 25
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Owen, J. L., Zhang, Y., Bae, S.-H., Farooqi, M. S., Liang, G., Hammer, R. E., Goldstein, J. L., & Brown, M. S. (2012). Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1213343109
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