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Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes
Open accessAbstract
Sterol regulatory element binding proteins (SREBPs) enhance transcription of genes encoding enzymes of cholesterol and fatty acid biosynthesis and uptake. In the current experiments, we observed a decline in the mRNA encoding one SREBP isoform, SREBP-1c, in the livers of rats that were rendered diabetic by treatment with streptozotocin. There was no change in the mRNA encoding SREBP-1a, which is derived from the same gene as SREBP-1c but uses a different promoter. The ratio of SREBP-1c:1a transcripts fell 25-fold from 5:1 in control rats to 0.2:1 in the diabetic animals. The SREBP-1c mRNA rose nearly to normal, and the 1c:1a ratio increased 17-fold when the diabetic rats were treated for 6 h with insulin. These treatments produced no change in the mRNA for SREBP-2, which is encoded by a separate gene. The SREBP-1c mRNA also fell selectively in freshly isolated rat hepatocytes and rose when the cells were treated with insulin. Considered together with recent data on hepatocytes [Foretz, M., Pacot, C., Dugal, I., et al. (1999) Mol. Cell. Biol. 19, 3760–3768], the current in vivo studies suggest that insulin may stimulate lipid synthesis in the liver by selectively inducing transcription of the SREBP-1c gene.
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Metadata
- Authors
- Shimomura, I., Bashmakov, Y., Ikemoto, S., Horton, J. D., Brown, M. S., & Goldstein, J. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-11-23
- Volume
- 96
- Issue
- 24
- Pages
- 13656-13661
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2030610610
- Cited by
- 793
- References
- 2
- FWCI
- 13.74
- Type
- journal article
- Language
- en
- Open access
- green
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