The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1
Open accessAbstract
Insulin rapidly lowers serum insulin-like growth factor-binding protein-1 (IGFBP-1) levels in vivo. In studies reported here, HEP G2 cells were used as a model system to investigate how insulin achieves this effect. When HEP G2 cells were incubated with 100 nM insulin for 6, 14, or 24 h, IGFBP-1 protein levels in conditioned medium fell to approximately 50% of control values. This apparently was due to a fall in the rate of IGFBP-1 protein synthesis, since HEP G2 cells incorporated 46% less [35S]methionine into IGFBP-1 during a 4-h incubation with 100 nM insulin. IGFBP-1 mRNA levels were similarly affected by 100 nM insulin, falling to 45% of control values after 2 h, and to 9% of control values after 4 h of incubation with this hormone. The fall in IGFBP-1 mRNA level is consistent with data from nuclear transcription assays. HEP G2 nuclei isolated from cells that were incubated with 100 nM insulin for 2 h synthesized only approximately 1/3 the number of IGFBP-1 transcripts as did control nuclei. Further evidence that insulin decreases IGFBP-1 gene transcription comes from transient transfections using chimeric IGFBP-1 promoter-chloramphenicol acetyltransferase reporter gene constructs. IGFBP-1 promoter activity fell to approximately 50% of control values when HEP G2 cells transfected with a construct containing the first 1205 base pairs of the IGFBP-1 promoter were incubated with 100 nM insulin for 6, 14, or 24 h. Insulin lowered both IGFBP-1 protein levels and promoter activity in a dose-dependent manner. A half-maximal effect was found at approximately 1 nM insulin and a maximal effect was found at approximately 10 nM insulin in each instance. Transfections with constructs containing smaller IGFBP-1 promoter fragments showed that the region spanning from 103 to 529 base pairs 5' to the IGFBP-1 mRNA cap site was necessary to demonstrate the inhibitory effect of insulin. These studies indicate that insulin lowers IGFBP-1 protein levels, at least in part, by rapidly decreasing the rate of IGFBP-1 gene transcription, and suggest that this insulin-mediated fall in transcription is conferred through a specific region of the IGFBP-1 promoter.
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“Insulin reduces the hepatic production of IGF binding protein (IGFBP)-1 (55,56) and possibly IGFBP-2 (57) with resultant increases in the levels of circulating free, bioactive IGF-I.”
From Diabetes and Cancer (2010) · cites this paper as [56]
In the citing paper
“Insulin reduces the hepatic production of IGF binding protein (IGFBP)-1 (55,56) and possibly IGFBP-2 (57) with resultant increases in the levels of circulating free, bioactive IGF-I.”
From Diabetes and Cancer (2010) · cites this paper as [56]
Citations
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Giovannucci, E., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · Diabetes Care · doi:10.2337/dc10-0666 · Cited by 2,366
Diabetes and Cancer: A Consensus Report
Giovannucci, E. L., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20078 · Cited by 1,082
Insulin, Insulin-Like Growth Factors and Colon Cancer: A Review of the Evidence
Giovannucci, E. (2001) · The Journal of Nutrition · doi:10.1093/jn/131.11.3109s · Cited by 959
Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets
Paoli, A., Rubini, A., Volek, J. S., & Grimaldi, K. A. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.116 · Cited by 885
Insulin-like Growth Factor Binding Proteins
Rechler, M. M. (1993) · Vitamins and hormones · doi:10.1016/s0083-6729(08)60444-6 · Cited by 759
Metadata
- Authors
- Powell, D. R., Suwanichkul, A., Cubbage, M. L., DePaolis, L. A., Snuggs, M. B., & Lee, P. D.
- Affiliations
- Baylor College of Medicine (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1991-10
- Volume
- 266
- Issue
- 28
- Pages
- 18868-18876
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1578799040
- Cited by
- 217
- References
- 49
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 9 · 2019: 5 · 2017: 2 · 2016: 8 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 6
- FWCI
- 9.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 38773)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- insulin, IGFBP-1, transcriptional repression, HepG2 cells, insulin signaling, gene expression regulation, promoter activity, dose-dependent effects, methionine incorporation, mRNA levels, transient transfection, chloramphenicol acetyltransferase
- MeSH terms
- Carrier Proteins, Gene Expression Regulation, Humans, Insulin, Insulin-Like Growth Factor I, Liver Neoplasms, Precipitin Tests, Promoter Regions, Genetic, Thymidine Kinase, Transcription, Genetic, Tumor Cells, Cultured, Insulin-Like Growth Factor Binding Proteins
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