Elsevier

Cellular Signalling

Volume 7, Issue 2, February 1995, Pages 85-91
Cellular Signalling

Topical review
Structural and functional heterogeneity of insulin receptors

https://doi.org/10.1016/0898-6568(94)00071-IGet rights and content

Abstract

It was long believed that the effects of insulin are mediated by a unique insulin receptor. However, there is considerable evidence suggesting that insulin receptors in brain, liver, adipocytes, and lymphocytes are heterogeneous in structure and function. This evidence is based on comparisons of concentration response curves in cells and tissues, and on comparisons of binding and effects of insulin-derivatives and receptor antibodies. Two receptor isoforms (IR-A and IR-B) generated by alternative mRNA splicing have been identified, but cannot fully account for the observed differences in ligand binding and receptor function. It is suggested that the differences in ligand binding reflect yet to be defined post-translational modifications, and that post-receptor events are responsible for the observed heterogeneity of insulin action.

References (42)

  • S. Gammeltoft et al.

    Biochim. biophys. Acta

    (1973)
  • S. Gammeltoft et al.

    J. biol. Chem.

    (1978)
  • H.G. Joost et al.

    Biochem. Pharmac.

    (1989)
  • S. Gammeltoft et al.

    Peptides

    (1984)
  • O. Sonne et al.

    J. biol. Chem.

    (1980)
  • R.A. Roth et al.

    J. biol. Chem.

    (1986)
  • J.F. Caro et al.

    Biochem. biophys. Res. Commun.

    (1988)
  • Y. Ebina et al.

    Cell

    (1985)
  • B. Vogt et al.

    Biochem. biophys. Res. Commun.

    (1991)
  • G. Sesti et al.

    Biochim. biophys. Res. Commun.

    (1991)
  • P.J. Smith et al.

    J. biol. Chem.

    (1988)
  • H. Kurachi et al.

    Biochem. biophys. Res. Commun.

    (1992)
  • C.C. Yip et al.

    Biochem. biophys. Res. Commun.

    (1980)
  • K.A. Heidenreich et al.

    J. biol. Chem.

    (1983)
  • K.B. Chiacchia

    Biochem. biophys. Res. Commun.

    (1991)
  • M. Fehlmann et al.

    Endocrinology

    (1981)
  • M. Weiland et al.
  • S. Gammeltoft

    Physiol. Rev.

    (1984)
  • M. Breiner et al.

    Molec. Pharmac.

    (1993)
  • A. Ullrich et al.

    Nature

    (1985)
  • D.E. Moller et al.

    Molec. Endocr.

    (1989)
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