Membrane glycoprotein PC-1 and insulin resistance

Ira D. Goldfine, Betty A. Maddux, Jack F. Youngren, Lucia Frittitta, Vincenzo Trischitta, G. Lynis Dohm

Research output: Contribution to journalArticle

Abstract

Peripheral resistance to insulin is a major component of non-insulin dependent diabetes mellitus. Defects in insulin receptor tyrosine kinase activity have been demonstrated in several tissues from insulin resistant subjects, but mutations in the insulin receptor gene occur in only a small fraction of cases. Therefore, other molecules that are capable of modulating the function of the insulin receptor are likely candidates in the search for the cellular mechanisms of insulin resistance. We have isolated an inhibitor of insulin receptor tyrosine kinase activity from cultured fibroblasts of an insulin resistant NIDDM patient and identified it as membrane glycoprotein PC-1. Subsequently we have demonstrated that expression of PC-1 is elevated in fibroblasts from other insulin resistant subjects, both with and without NIDDM. Studies in muscle, the primary site for insulin-mediated glucose disposal, have shown that the levels of PC-1 in this tissue are inversely correlated to insulin action both in vivo and in vitro. Transfection of PC-1 into cultured cells has confirmed that overexpression of PC-1 can produce impairments in insulin receptor tyrosine kinase activity and the subsequent cellular responses to insulin. Preliminary data suggests a direct interaction between PC-1 and the insulin receptor. However, the mechanisms whereby PC-1 inhibits insulin receptor signaling remain to be determined.

Original languageEnglish
Pages (from-to)177-184
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume182
Issue number1-2
DOIs
Publication statusPublished - 1998

Keywords

  • Diabetes mellitus
  • Hyperglycemia
  • Insulin receptor
  • Membrane glycoprotein
  • Tyrosine kinase

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Goldfine, I. D., Maddux, B. A., Youngren, J. F., Frittitta, L., Trischitta, V., & Dohm, G. L. (1998). Membrane glycoprotein PC-1 and insulin resistance. Molecular and Cellular Biochemistry, 182(1-2), 177-184. https://doi.org/10.1023/A:1006878001180