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Journal Article| Volume 266, ISSUE 28, P18868-18876, October 05, 1991

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

Open AccessPublished:October 05, 1991DOI:https://doi.org/10.1016/S0021-9258(18)55144-9
Insulin inhibits transcription of the human gene for insulin-like growth factor-binding protein-1.
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      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.

      References

        • Baxter R.C.
        • Martin J.L.
        Prog. Growth Factor Res. 1989; 1: 49-68
        • Mohan S.
        • Bautista C.M.
        • Wergedal J.
        • Baylink D.J.
        Proc. Natl. Acad. Sci. U. S. A. 1989; 86: 8338-8342
        • Roghani M.
        • Hossenlopp P.
        • Lepage P.
        • Balland A.
        • Binoux M.
        FEES Lett. 1989; 255: 253-258
        • Ritvos O.
        • Ranta T.
        • Jalkanen J.
        • Suikkari A.-M.
        • Voutilainen R.
        • Bohn H.
        • Rutanen E.-M.
        Endocrinology. 1988; 122: 2150-2157
        • Frauman A.G.
        • Tsuzaki S.
        • Moses A.C.
        Endocrinology. 1989; 124: 2289-2296
        • Burch W.M.
        • Correa J.
        • Shively J.E.
        • Powell D.R.
        J. Clin. Endocrinol. Metab. 1990; 70: 173-180
        • Conover C.A.
        • Ronk M.
        • Lombana F.
        • Powell D.R.
        Endocrinology. 1990; 127: 2795-2803
        • Elgin R.G.
        • Busby Jr, W.H.
        • Clemmons D.R.
        Proc. Natl. Acad. Sci. U. S. A. 1987; 84: 3254-3258
        • Drop S.L.S.
        • Kortleve D.J.
        • Guyda H.J.
        • Posner B.I.
        J. Clin. Endocrinol. Metab. 1984; 59: 908-915
        • Baxter R.C.
        • Cowell C.T.
        J. Clin. Endocrinol. Metab. 1987; 65: 432-440
        • Conover C.A.
        • Butler P.C.
        • Wang M.
        • Rizza R.A.
        • Lee P.D.K.
        Diabetes. 1990; 39: 1251-1256
        • Holly J.M.P.
        • Biddlecombe R.A.
        • Dunger D.B.
        • Edge J.A.
        • Amiel S.A.
        • Howell R.
        • Chard T.
        • Rees L.H.
        • Wass J.A.H.
        Clin. Endocrinol. 1988; 29: 667-675
        • Cotterill A.M.
        • Cowell C.T.
        • Baxter R.C.
        • McNeil D.
        • Silinik M.
        J. Clin. Endocrinol. Metab. 1988; 67: 882-887
        • Suikkari A.-M.
        • Koivisto V.A.
        • Rutanen E.-M.
        • Yki-Jarvinen H.
        • Karonen S.L.
        • Seppala M.
        J. Clin. Endocrinol. Metab. 1988; 66: 266-272
        • Busby W.H.
        • Snyder D.K.
        • Clemmons D.R.
        J. Clin. Endocrinol. Metab. 1988; 67: 1225-1230
        • Yeoh S.I.
        • Baxter R.C.
        Acta Endocrinol. 1988; 119: 465-473
        • Brismar K.
        • Gutniak M.
        • Povoa G.
        • Werner S.
        • Hall K.
        J. Endocrinol. Invest. 1988; 11: 599-602
        • Lewitt M.S.
        • Baxter R.C.
        J. Clin. Endocrinol. Metab. 1989; 69: 246-252
        • Conover C.A.
        • Lee P.D.K.
        J. Clin. Endocrinol. Metab. 1990; 70: 1062-1067
        • Ooi G.T.
        • Orlowski C.C.
        • Brown A.L.
        • Becker R.E.
        • Unterman T.G.
        • Rechler M.M.
        Mol. Endocrinol. 1990; 4: 321-328
        • Unterman T.G.
        • Patel K.
        • Mahathre V.K.
        • Rajamohan G.
        • Oehler D.T.
        • Becker R.E.
        Endocrinology. 1990; 126: 2614-2624
        • Kelly J.H.
        • Darlington G.J.
        In Vitro. 1989; 25: 217-222
        • Powell D.R.
        • Lee P.D.K.
        • Shively J.E.
        • Eckenhausen M.
        • Hintz R.L.
        J. Chromatogr. 1987; 420: 163-170
        • Powell D.R.
        • Suwanichkul A.
        • Cubbage M.L.
        Drop S.L.S. Hintz R.L. Insulin-like Growth Factor Binding Proteins. Elsevier Science Publishers B. V., Amsterdam1989: 3-8
        • Suwanichkul A.
        • Cubbage M.L.
        • Powell D.R.
        J. Biol. Chem. 1990; 265: 21185-21193
        • Jacoby D.B.
        • Zilz N.D.
        • Towle H.C.
        J. Biol. Chem. 1989; 264: 17623-17626
        • Nordeen S.K.
        Biotechniques. 1988; 6: 454-457
        • Graham F.L.
        • Van der Eb A.J.
        Virology. 1973; 52: 456-467
        • deWet J.R.
        • Wood K.V.
        • de Luca M.
        • Helinski D.R.
        • Subramani S.
        Mol. Cell Biol. 1987; 7: 725-737
        • Gorman C.M.
        • Moffat L.F.
        • Howard B.H.
        Mol. Cell. Biol. 1982; 2: 1044-1051
        • Cubbage M.L.
        • Suwanichkul A.
        • Powell D.R.
        Mol. Endocrinol. 1989; 3: 846-851
        • Cubbage M.L.
        • Suwanichkul A.
        • Powell D.R.
        J. Biol. Chem. 1990; 265: 12642-12649
        • Lee P.D.K.
        • Hintz R.L.
        • Sperry J.B.
        • Baxter R.C.
        • Powell D.R.
        Pediatr. Res. 1989; 26: 308-315
        • Liu F.
        • Powell D.R.
        • Hintz R.L.
        J. Clin. Endocrinol. Metab. 1990; 70: 620-628
        • Harlow E.
        • Lane D.
        Antibodies. 1st ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1988: 139-281
        • Moss M.
        • Schwartz R.J.
        Mol. Cell. Biol. 1981; 1: 289-301
        • Lee Y.-L.
        • Hintz R.L.
        • James P.M.
        • Lee P.D.K.
        • Shively J.E.
        • Powell D.R.
        Mol. Endocrinol. 1988; 2: 404-411
        • Cleveland D.W.
        • Lopata M.A.
        • MacDonald R.J.
        • Cowan N.J.
        • Rutter W.J.
        • Kirschner M.W.
        Cell. 1980; 20: 95-105
        • Fehlmann M.
        • Crettaz M.
        • Kahn C.R.
        Biochem. J. 1983; 214: 845-850
        • Short J.M.
        • Wynshaw-Boris A.
        • Short H.
        • Hanson R.W.
        J. Biol. Chem. 1986; 261: 9721-9726
        • Orlowski C.C.
        • Ooi G.T.
        • Rechler M.M.
        Mol. Endocrinol. 1990; 4: 1592-1599
        • Seneviratne C.
        • Luo J.
        • Murphy L.J.
        Mol. Endocrinol. 1990; 4: 1199-1204
        • Prager D.
        • Melmed S.
        J. Biol. Chem. 1988; 263: 16580-16585
        • O'Brien R.M.
        • Lucas P.C.
        • Forest C.D.
        • Magnuson M.A.
        • Granner D.K.
        Science. 1990; 249: 533-537
        • Sasaki K.
        • Cripe T.P.
        • Koch S.R.
        • Andreone T.L.
        • Petersen D.D.
        • Beale E.G.
        • Granner D.K.
        J. Biol. Chem. 1984; 259: 15242-15251
        • Magnuson M.A.
        • Quinn P.G.
        • Granner D.K.
        J. Biol. Chem. 1987; 262: 14917-14920
        • Jefferson L.S.
        Diabetes. 1980; 29: 487-496
        • Dani C.
        • Bertrand B.
        • Bardon S.
        • Doglio A.
        • Amri E.
        • Grimaldi P.
        Mol. Cell. Endocrinol. 1989; 63: 199-208
        • Imai E.
        • Stromstedt P.-E.
        • Quinn P.G.
        • Carlstedt-Duke J.
        • Gustafsson J.-A.
        • Granner D.K.
        Mol. Cell. Biol. 1990; 10: 4712-4719
        • Roesler W.J.
        • Park E.A.
        • Klemm D.J.
        • Liu J.
        • Gurney A.L.
        • Vandenbark G.R.
        • Hanson R.W.
        Trends Endocrinol. Metab. 1990; 1: 347-351

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      Published online: October 05, 1991

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      DOI: https://doi.org/10.1016/S0021-9258(18)55144-9

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      © 1991 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.

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