Abstract
The sequence of events for insulin action on its target cells is schematically represented in Fig. 2.1. After being secreted by the pancreatic α cells, insulin travels in the plasma to target cells throughout the body, where it binds rapidly and reversibly to a finite number of receptors on the external surface of the plasma membrane. The receptor serves two functions. First, the receptor recognizes insulin from among all the other substances to which the cell is being exposed; it manifests its recognition by binding to the hormone. Second, the hormone-receptor complex begins the activation at the target cell that leads ultimately to the multiplicity of effects that insulin produces on any of its target cells. It is widely believed that insulin action on its target cells is mediated by a soluble intracellular messenger that functions to carry out all the effects of insulin. While it is clear that cyclic AMP is not the second messenger for insulin, it is suspected that the second messenger for insulin functions in a manner analogous to that described for cyclic AMP (Roth, 1979a). Recent studies by two laboratories have provided evidence for the existence of a second messenger for insulin, a soluble product thought to be produced from endogenous components of the target cell that carries out fundamental actions of insulin, such as enzyme activation and inactivation (Seal and Jarrett, 1980; Larner et al., 1980).
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References
Arndt-Jovin, D.J., Ostertag, W., Wisen, H., Klimek, F. and Jovin, T. (1976), J. Histochem. Cytochem., 24, 332–347.
Bar, R.S., Koren, H. and Roth, J. (1976), Diabetes, 25, Suppl. I, 348.
Barazzone, P., Carpentier, J.-L., Gorden, P., Van Obberghen, E. and Orci, L. (1980), Nature., 286, 401–403.
Bergeron, J.J.M., Evans, W.H. and Geschwind, I.I. (1973), J. Cell Biol., 59, 771–776.
Bergeron, J.J.M., Sikstrom, R., Hand, A.R. and Posner, B.I. (1979), J. Cell Biol., 80, 427–443.
Blackard, W.G., Guzelian, P.S. and Small, M.E. (1978), Endocrinology., 103, 548–554.
Carpentier, J.-L., Gorden, P., Amherdt, M., Van Obberghen, E., Kahn, C.R. and Orci, L. (1978), J. Clin. Invest., 61, 1057–1070.
Carpentier, J.-L., Gorden, P., Freychet, P., LeCam, A. and Orci, L. (1979), J. Clin. Invest., 63, 1249–1261.
Carpentier, J.-L., Van Obberghen, E., Gorden, P. and Orci, L. (1980), Diabetologia., 19, 263.
Catt, K.J. and Dufau, M.L. (1977), Annu. Rev. Physiol., 39, 529–557.
Catt, K.J., Harwood, J.P., Aguilera, G. and Dufau, M.L. (1979), Nature., 280, 109–116.
Chang, T.H. and Polakis, S.E. (1978), J. Biol. Chem., 253, 4693–4696.
Cuatrecasas, P. (1971), J. Biol. Chem., 246, 6532–6542.
Cuatrecasas, P. (1972), J. Biol. Chem., 247, 1980–1991.
Cuatrecasas, P. (1974), Annu. Rev. Biochem., 43, 169–214.
Cuatrecasas, P. and Tell, G.P.E. (1973), Proc. Natl. Acad. Sci. USA., 71, 485–489.
De Meyts, P. (1976), in Methods in Receptor Research (Blecher, M., ed), Marcel Dekker, New York, pp. 301–383.
De Meyts, P. (1976), J. Supramolec. Struct., 4, 241–258.
De Meyts, P. (1980), in Hormones and Cell Regulation (Dumont, J. and Nunez, J., eds), in press.
De Meyts, P. and Roth, J. (1975), Biochem. Biophys. Res. Commun., 66, 1118–1126.
De Meyts, P., Roth, J., Neville, D.M., Jr., Gavin, J.R., III and Lesniak, M.A. (1973), Biochem. Biophys. Res. Commun., 55, 154–161.
De Meyts, P., Bianco, A.R. and Roth, J. (1976), J. Biol. Chem., 251, 1877–1888.
De Meyts, P., Van Obberghen, E., Roth, J., Wollmer, A. and Brandenberg, D. (1978), Nature., 273, 504–509.
Desbuquois, B. and Aurbach, G.D. (1971), J. Clin. Endocrinol. Metab., 33, 732–738.
Devreotes, P.N., Gardner, J.M. and Fambrough, D.M. (1977), Cell., 10, 365–373.
Fambrough, D.M. and Devreotes, P.N. (1976), in Biogenesis and Turnover of Membrane Macromolecules (Cook, J.S., ed.), Raven Press, New York, pp. 124–144.
Flier, J.S., Kahn, C.R., Roth, J. and Bar, R.S. (1975), Science., 190, 63–65.
Freychet, P., Roth, J. and Neville, D.M., Jr., (1971), Proc. Natl. Acad. Sci. USA., 68, 1833–1837.
Freychet, P., Brandenburg, D. and Wollmer, A. (1975), Diabetologia., 10, 1–5.
Friend, C., Scher, W., Holland, J.G. and Sato, T. (1971), Proc. Natl. Acad. Sci. USA., 68, 378–382.
Gavin, J.R., III, Mann, D.L., Buell, D.N. and Roth, J. (1972), Biochem. Biophys. Res. Commun., 49, 870–876.
Gavin, J.R., III, Gorden, P., Roth, J., Archer, J.A. and Buell, D.N. (1973), J. Biol. Chem., 248, 2202–2207.
Gavin, J.R., III, Roth, J., Neville, D.M., Jr., De Meyts, P. and Buell, D.N. (1974), Proc. Natl. Acad. Sci. USA., 71, 84–88.
Germinario, R.H., Kleiman, L., Peters, S. and Olivera, M. (1977), Exp. Cell Res., 110, 375–385.
Ginsberg, B.H. (1977), in Biochemical Actions of Hormones (Litwak, G., ed.), Vol. 4, Academic Press, New York, pp. 313–349.
Ginsberg, B.H., Kahn, C.R., Roth, J. and De Meyts, P.(1976), Biochem. Biophys. Res. Commun., 73, 1068–1074.
Ginsberg, B.H., Brown, T. and Raizada, M. (1979), Diabetes., 28, 823–827.
Gliemann, J. and Gammeltoft, S. (1974), Diabetologia., 10, 105–113.
Goldfine, I.D. and Smith, G.J. (1976), Proc. Natl. Acad. Sci. USA., 73, 1427–1431.
Goldfine, I.D., Jones, A.L., Hradek, G.T., Wong, K.Y. and Mooney, J.S. (1978), Science., 202, 760–763.
Goldstein, J.L., Anderson, R.G.W. and Brown, M.S. (1979), Nature., 279, 679–684.
Goodfriend, T.L. and Lin, S.-Y. (1970), Circ. Res., 26/27, 1–163—I-174, Suppl. 1.
Gorden, P., Carpentier, J.-L., Freychet, P., LeCam, A. and Orci, L. (1978), Science., 200, 782–785.
Gorden, P., Carpentier, J.-L., Van Obberghen, E., Barazzone, P., Roth, J. and Orci, L. (1979), J. Cell Sci., 39, 77–88.
Gorden, P., Carpentier, J.-L., Freychet, P. and Orci, L. (1980), Diabetologia., 18, 263–274.
Green, H. and Kehinde, O. (1974), Cell., 1, 113–116.
Green, H. and Kehinde, O. (1975), Cell., 5, 19–27.
Green, H. and Kehinde, O. (1976), Cell., 7, 105–113.
Green, H. and Meuth, M. (1974), Cell., 3, 127–131.
Grimaldi, P., Négrel, R., Vincent, J.P. and Ailhaud, G. (1979), J. Biol. Chem., 254, 6849–6852.
Harmon, J.T., Kahn, C.R., Kempner, E.J. and Schlegel, W. (1980), J. Biol. Chem., 255, 3412–3419.
Harrison, L.C. and Kahn, C.R. (1980), Prog. Clin. Immunol., 4, 107–125.
Harrison, L.C., Flier, J.S., Itin, A., Kahn, C.R. and Roth, J. (1979), Science., 203, 544–547.
Hauger, R.L., Aguilera, G. and Catt, K.J. (1978), Nature., 271, 176–177.
Helderman, J.H. and Strom, T.B. (1977), J. Clin. Invest., 59, 338–344.
Helderman, J.H. and Strom, T.B. (1978a), Nature., 274, 62–63.
Helderman, J.H. and Strom, T.B. (1978b), Abstr. 7th Int. Congr. Nephr., J-l.
Helderman, J.H. and Strom, T.B. (1979), J. Biol. Chem., 254, 7203–7207.
Helderman, J.H., Reynolds, T.C. and Strom, T.B. (1978), Eur. J. Immunol., 8, 589–595.
Hinkle, P.M. and Tashijian, A.H. Jr. (1976), Biochemistry., 14, 3845–3851.
Horvat, A., Li, E. and Katsoyannis, P.G. (1975), Biochim. Biophys. Acta., 382, 609–620.
Jarett, L. and Smith, R.M. (1977), J. Supramol. Struct., 6, 45–59.
Jarrett, D.B., Roth, J., Kahn, C.R. and Flier, J.S. (1976), Proc. Natl. Acad. Sci. USA., 73, 4115–4119.
Kahn, C.R. (1976), J. Cell Biol., 70, 261–286.
Kahn, C.R., Neville, D.M., Jr., and Roth, J. (1973), J. Biol. Chem., 248, 244–250.
Kahn, C.R., Freychet, P., Neville, D.M., Jr. and Roth, J. (1974), J. Biol. Chem., 249, 2249–2257.
Kahn, C.R., Flier, J.S., Bar, R.S., Archer, J.A., Gorden, P., Martin, M.M. and Roth, J. (1976), N. Engl. J. Med., 294, 739–745.
Karlsson, F. A., Grunfeld, C., Kahn, C.R. and Roth, J. (1978), Endocrinology., 104, 1383–1392.
Karlsson, F.A., Grunfeld, C., Kahn, C.R. and Roth, J. (1979), Program and Abstracts 60th Annual Meeting of the Endocrine Society, p. 161, abstract 174.
Kasuga, O., Van Obberghen, E., Yamada, K. and Harrison, L.C. (1981), Diabetes., in press.
Kobayashi, M. and Olefsky, J.H. (1978), J. Clin. Invest., 62, 73–81.
Kono, T. (1971), J. Biol. Chem., 244, 5777–5784.
Kono, T. and Barham, F.S. (1971), J. Biol. Chem., 246, 6210–6216.
Kosmakos, F. and Roth, J. (1980), J. Biol. Chem., 20, 9860–9869.
Krug, U., Krug, F. and Cuatrecasas, P. (1972), Proc. Natl. Acad. Sci. USA., 69, 2604–2608.
Kuri-Harcuch, W. and Green, H. (1977), J. Biol. Chem., 252, 2158–2160.
Kuri-Harcuch, W. and Green, H. (1978), Proc. Natl. Acad. Sci. USA., 75, 6107–6109.
Kuri-Harcuch, W., Wise, L.S. and Green, H. (1978), Cell., 14, 53–59.
Lang, U., Kahn, C.R. and Chrambach, A. (1979), Endocrinology., 106, 40–49.
Larner, J., Galasko, G., Cheng, K., De Paoli-Roach, A.A., Huang, L., Daggy, P. and Kellogg, J. (1980), Science., 206, 1408–1410.
Lefkowitz, R.J., Pastan, I. and Roth, J. (1969), in The Role of Adenyl Cyclase and Cyclic 3′, 5′-AMP in Biological Systems, (Rall, T.W., Rodbell, M. and Condliffe, P., eds), NIH Fogarty International Center Proceedings, Bethesda, Maryland.
Lefkowitz, R.J., Roth, J., Pricer, W. and Pastan, I. (1980), Proc. Natl. Acad. Sci. USA., 65, 745–762.
Lesniak, M.A. and Roth, J. (1976), J. Biol. Chem., 251, 3720–3729.
Lesniak, M.A., Gorden, P. and Roth, J. (1977), J. Clin. Endocrinol. Metab. 44, 838–849.
Lin, S.-Y. and Goodfriend, T.L. (1970), Amer. J. Physiol., 218, 1319–1328.
Mackall, J.C., Student, A.K., Polakis, S.E. and Lane, M.D. (1976), J. Biol. Chem., 251, 6462–6464.
Maturo, J.M. and Hollenberg, M.D. (1978), Proc. Natl. Acad. Sci. USA., 75, 3070–3074.
Mott, D.M., Howard, B.V. and Bennett, P.H. (1979), J. Biol. Chem., 254, 8762–8767.
Mukherjee, C., Caron, M.C. and Lefkowitz, R. (1975), Proc. Natl. Acad. Sci. USA., 72, 1945–1949.
Négrel, R., Grimaldi, P. and Ailhaud, G. (1978), Proc. Natl. Acad. Sci. USA., 75, 6054–6058.
Newerly, K. and Berson, S.A. (1957), Proc. Soc. Exp. Biol. Med., 94, 751–755.
Orci, L., Rufener, C., Malaisse-Lagae, F., Blondel, B., Amherdt, M., Bataille, D., Freychet, P. and Perrelet, A. (1975), Isr. J. Med. Sci., 11, 639–655.
Pastan, I., Johnson, G.S. and Anderson, W.B. (1975), Annu. Rev. Biochem., 44, 491–522.
Pilch, P.F. and Czech, M.P. (1980), J. Biol. Chem., 255, 1722–1731.
Pollet, R.J., Standaert, M.L. and Haase, B.A. (1977), J. Biol. Chem., 252, 5828–5834.
Podskalny, J.M., Chou, J.Y. and Rechler, M.M. (1975), Arch. Biochem. Biophys., 170, 504–513.
Posner, B.I. (1974), Diabetes., 23, 209–217.
Posner, B.I., Kelly, P.A. and Friesen, H.G. (1975), Science., 188, 57–59.
Raff, M. (1976), Nature., 250, 265–266.
Reed, B.C. and Lane, D.M. (1980), Proc. Natl. Acad. Sci. USA., 77, 285–289.
Reed, B.C., Kaufman, S.H., Mackall, J.C., Student, A.K. and Lane, M.D. (1977), Proc. Natl. Acad. Sci. USA., 74, 4876–4880.
Rosen, O.M., Chia, G.H., Fung, C. and Rubin, C.S. (1979), J. Cell Physiol., 99, 37–42.
Ross, J., Gielen, J., Packman, S., Ikawa, Y. and Leder, P. (1974), J. Mol. Biol., 87, 697–714.
Roth, J. (1973), Metabolism., 22, 1059–1073.
Roth, J. (1979a), in Endocrinology, Vol. 3 (De Groot, L., ed.), Grune and Stratton, New York, pp. 2037–2054.
Roth, J. (1979b), in Developments in Cell Biology, Vol. 4 (Delisi, C. and Blumenthal, R., eds), Elsevier North Holland, Inc., Amsterdam, pp. 185–196.
Rubin, C.S., Lai, E. and Rosen, O.M. (1977), J. Biol. Chem., 252, 3554–3557.
Rubin, C.S., Hirsch, A., Fung, C. and Rosen, O.M. (1978), J. Biol. Chem., 253, 7570–7578.
Russell, T.R. and Ho, R.-J. (1976), Proc. Natl. Acad. Sci. USA., 73, 4516–4520.
Sassa, S. (1976), J. Exp. Med., 43, 305–315.
Scher, W., Holland, J.G. and Friend, C. (1971), Blood., 37, 428–437.
Schlessinger, J. (1980), Trends in Biochemical Sciences., 5, 210–214.
Schlessinger, J., Schechter, Y., Willingham, M.C. and Pastan, I. (1978), Proc. Natl. Acad. Sci. USA., 75, 2659–2663.
Schlessinger, J., Van Obberghen, E. and Kahn, C.R. (1980), Nature., 286, 729–731.
Seals, J.R. and Jarett, L. (1980), Proc. Natl. Acad. Sci. USA., 77, 77–81.
Spooner, P.M., Chernick, S.S., Garrison, M.M. and Scow, R. (1979), J. Biol. Chem., 254, 1305–1311.
Srikanrt, C.B., Freeman, D., McCorkle, K. and Unger, R. (1977), J. Biol. Chem., 252, 7434–7436.
Stadie, W.C., Haugaard, N. and Vaughan, M.J. (1953), J. Biol. Chem., 200, 745–751.
Strom, T.B., Helderman, J.H. and Williams, R.M. (1978), Immunogenetics., 7, 51–56.
Suzuki, K. and Kono, T. (1979), J. Biol. Chem., 254, 9786–9794.
Terris, S. and Steiner, D.F. (1975), J. Biol. Chem., 250, 8389–8398.
Thompoulos, P., Roth, J., Lovelace, E. and Pastan, I. (1976), Cell., 8, 417–423.
Thomopoulos, P., Kosmakos, F.C., Pastan, I. and Lovelace, E. (1977), Biochem. Biophys. Res. Commun., 75, 246–252.
Thomopoulos, P., Berthellier, M. and Laudat, M.H. (1978), Biochem. Biophys. Res Commun., 85, 1460–1464.
Todaro, G.J. and Green, H. (1963), J. Cell Biol., 17, 299–313.
Wachslicht-Rodbard, H., Zeleznik, A.J., McGuire, E.A., Berman, M., Rodbard, D. and Roth, J., in preparation.
Waelbroeck, M., Van Obberghen, E. and De Meyts, P. (1979), J. Biol. Chem., 254, 7736–7740.
Williams, I.H. and Polakis, S.E. (1977), Biochem. Biophys. Res. Commun., 77, 175–186.
Wise, L.S. and Green, H. (1978), Cell., 13, 233–242.
Wisher, M.H., Baron, M.D., Jones, R.H., Sonksen, P.H., Saunders, D.J., Thamm, P. and Brandenburg, D. (1980), Biochem. Biophys. Res. Commun., 92, 492–498.
Yip, C.C., Yeung, C.W.T. and Moule, M.L. (1978), J. Biol. Chem., 253, 1743–1745.
Yip, C.C., Yeung, C.W.T. and Moule, M.L. (1980), Biochemistry., 19, 70–76.
Zeleznik, A.J. and Roth, J. (1978), J. Clin. Invest., 61, 1363–1374.
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van Obberghen, E., Roth, J. (1981). The Insulin Receptor and its Function. In: Lefkowitz, R.J. (eds) Receptor Regulation. Receptors and Recognition. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-5822-7_2
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