Cited by 217Growth Hormone and Insulin-like Growth FactorsGenomics and Chromatin DynamicsEstrogen and related hormone effects

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Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1

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Powell, D.R., Suwanichkul, A., Cubbage, M.L., DePaolis, L.A., Snuggs, M.B., Lee, P.D.·1991·Journal of Biological Chemistry

DOI 10.1016/s0021-9258(18)55144-9

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Abstract

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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Authors: Powell, D. R., Suwanichkul, A., Cubbage, M. L., DePaolis, L. A., Snuggs, M. B., & Lee, P. D.
Affiliations: Baylor College of Medicine (US)
ORCID: Powell, D.R.
Lee, P.D.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1991-10
Volume: 266
Issue: 28
Pages: 18868-18876
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1016/s0021-9258(18)55144-9
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 10606 d)
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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Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1

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