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Proc Natl Acad Sci U S A. 1984 Jul; 81(13): 4028–4032.
PMCID: PMC345361
PMID: 6330732

Insulin activates the appearance of insulin-like growth factor II receptors on the adipocyte cell surface.

Abstract

To evaluate the mechanism of insulin action to increase rat 125I-labeled insulin-like growth factor II (125I-IGF-II) binding to rat adipocytes, we raised a potent rabbit antiserum against purified IGF-II receptors from rat placental membranes. The antiserum elicited a positive reaction at a 1:5000 dilution against purified IGF-II receptor in an ELISA and markedly inhibited 125I-IGF-II binding to adipocyte plasma membranes when added prior to the growth factor. Immunoprecipitation lines formed between agar plate wells containing antiserum versus IGF-II receptor, both in the presence and absence of 1 microM IGF-II, indicating that binding of anti-receptor Ig to the IGF-II receptor is not affected by occupancy of the IGF-II binding site. Intact adipocytes treated with or without insulin were incubated with anti-IGF-II receptor Ig, washed, and further incubated with 125I-labeled goat anti-rabbit IgG to monitor the amount of anti-receptor Ig bound. Insulin induced parallel increases in anti-IGF-II receptor Ig binding (2.4-fold) and 125I-IGF-II binding (3-fold) to the isolated cells. The dose-response relationship of insulin action on 125I-IGF-II binding and anti-receptor Ig binding was essentially identical with a half-maximal effect at approximately 0.07 nM insulin. That insulin does not act to expose new types of antigenic sites on IGF-II receptors was indicated by the demonstration that control adipocytes could readily adsorb the anti-receptor Ig. These data demonstrate that increased numbers of IGF-II receptors are displayed in an exposed position on the adipocyte cell surface in response to insulin.

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  • Zapf J, Rinderknecht E, Humbel RE, Froesch ER. Nonsuppressible insulin-like activity (NSILA) from human serum: recent accomplishments and their physiologic implications. Metabolism. 1978 Dec;27(12):1803–1828. [PubMed] [Google Scholar]
  • Rinderknecht E, Humbel RE. Primary structure of human insulin-like growth factor II. FEBS Lett. 1978 May 15;89(2):283–286. [PubMed] [Google Scholar]
  • Zapf J, Schoenle E, Froesch ER. Insulin-like growth factors I and II: some biological actions and receptor binding characteristics of two purified constituents of nonsuppressible insulin-like activity of human serum. Eur J Biochem. 1978 Jun 15;87(2):285–296. [PubMed] [Google Scholar]
  • Rechler MM, Nissley SP, King GL, Moses AC, Van Obberghen-Schilling EE, Romanus JA, Knight AB, Short PA, White RM. Multiplication stimulating activity (MSA) from the BRL 3A rat liver cell line: relation to human somatomedins and insulin. J Supramol Struct Cell Biochem. 1981;15(3):253–286. [PubMed] [Google Scholar]
  • Massague J, Guillette BJ, Czech MP. Affinity labeling of multiplication stimulating activity receptors in membranes from rat and human tissues. J Biol Chem. 1981 Mar 10;256(5):2122–2125. [PubMed] [Google Scholar]
  • Massagué J, Czech MP. The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem. 1982 May 10;257(9):5038–5045. [PubMed] [Google Scholar]
  • Kasuga M, Van Obberghen E, Nissley SP, Rechler MM. Demonstration of two subtypes of insulin-like growth factor receptors by affinity cross-linking. J Biol Chem. 1981 Jun 10;256(11):5305–5308. [PubMed] [Google Scholar]
  • Massague J, Pilch PF, Czech MP. Electrophoretic resolution of three major insulin receptor structures with unique subunit stoichiometries. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7137–7141. [PMC free article] [PubMed] [Google Scholar]
  • Jacobs S, Cuatrecasas P. Insulin receptor: structure and function. Endocr Rev. 1981 Summer;2(3):251–263. [PubMed] [Google Scholar]
  • Oppenheimer CL, Czech MP. Purification of the type II insulin-like growth factor receptor from rat placenta. J Biol Chem. 1983 Jul 25;258(14):8539–8542. [PubMed] [Google Scholar]
  • August GP, Nissley SP, Kasuga M, Lee L, Greenstein L, Rechler MM. Purification of an insulin-like growth factor II receptor from rat chondrosarcoma cells. J Biol Chem. 1983 Aug 10;258(15):9033–9036. [PubMed] [Google Scholar]
  • King GL, Kahn CR, Rechler MM, Nissley SP. Direct demonstration of separate receptors for growth and metabolic activities of insulin and multiplication-stimulating activity (an insulinlike growth factor) using antibodies to the insulin receptor. J Clin Invest. 1980 Jul;66(1):130–140. [PMC free article] [PubMed] [Google Scholar]
  • King GL, Rechler MM, Kahn CR. Interactions between the receptors for insulin and the insulin-like growth factors on adipocytes. J Biol Chem. 1982 Sep 10;257(17):10001–10006. [PubMed] [Google Scholar]
  • Oppenheimer CL, Pessin JE, Massague J, Gitomer W, Czech MP. Insulin action rapidly modulates the apparent affinity of the insulin-like growth factor II receptor. J Biol Chem. 1983 Apr 25;258(8):4824–4830. [PubMed] [Google Scholar]
  • Massagué J, Blinderman LA, Czech MP. The high affinity insulin receptor mediates growth stimulation in rat hepatoma cells. J Biol Chem. 1982 Dec 10;257(23):13958–13963. [PubMed] [Google Scholar]
  • Cushman SW, Wardzala LJ. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J Biol Chem. 1980 May 25;255(10):4758–4762. [PubMed] [Google Scholar]
  • Suzuki K, Kono T. Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc Natl Acad Sci U S A. 1980 May;77(5):2542–2545. [PMC free article] [PubMed] [Google Scholar]
  • Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry. 1971 Sep;8(9):871–874. [PubMed] [Google Scholar]
  • Voller A, Bartlett A, Bidwell DE. Enzyme immunoassays with special reference to ELISA techniques. J Clin Pathol. 1978 Jun;31(6):507–520. [PMC free article] [PubMed] [Google Scholar]
  • RODBELL M. METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS. J Biol Chem. 1964 Feb;239:375–380. [PubMed] [Google Scholar]
  • Gliemann J. Insulin-like activity of dilute human serum assayed by an isolated adipose cell method. Diabetes. 1965 Oct;14(10):643–649. [PubMed] [Google Scholar]
  • McKeel DW, Jarett L. Preparation and characterization of a plasma membrane fraction from isolated fat cells. J Cell Biol. 1970 Feb;44(2):417–432. [PMC free article] [PubMed] [Google Scholar]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  • Marquardt H, Todaro GJ, Henderson LE, Oroszlan S. Purification and primary structure of a polypeptide with multiplication-stimulating activity from rat liver cell cultures. Homology with human insulin-like growth factor II. J Biol Chem. 1981 Jul 10;256(13):6859–6865. [PubMed] [Google Scholar]
  • Pilch PF, Axelrod JD, Colello J, Czech MP. Unimpaired signal transduction by the adipocyte insulin receptor following its partial proteolytic fragmentation. J Biol Chem. 1981 Feb 25;256(4):1570–1575. [PubMed] [Google Scholar]
  • Gliemann J, Osterlind K, Vinten J, Gammeltoft S. A procedure for measurement of distribution spaces in isolated fat cells. Biochim Biophys Acta. 1972 Nov 24;286(1):1–9. [PubMed] [Google Scholar]
  • LaBarbera AR, Ryan RJ. Porcine granulosa cells in suspension culture. I. follicle-stimulating hormone induction of human chorionic gonadotropin-binding sites on cells from small follicles. Endocrinology. 1981 Apr;108(4):1561–1570. [PubMed] [Google Scholar]
  • Stadel JM, Nambi P, Shorr RG, Sawyer DF, Caron MG, Lefkowitz RJ. Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the beta-adrenergic receptor. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3173–3177. [PMC free article] [PubMed] [Google Scholar]
  • Pessin JE, Gitomer W, Oka Y, Oppenheimer CL, Czech MP. beta-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes. J Biol Chem. 1983 Jun 25;258(12):7386–7394. [PubMed] [Google Scholar]

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