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Role of PC-1 in the etiology of insulin resistance

I D Goldfine1, B A Maddux, J F Youngren

  • 1Department of Medicine, Mount Zion Medical Center, University of California San Francisco 94143-1616, USA. idg@itsa.ucsf.edu

Annals of the New York Academy of Sciences
|June 8, 2000
PubMed

Insights

Membrane glycoprotein PC-1 inhibits insulin receptor activity, contributing to insulin resistance. Elevated PC-1 levels are linked to reduced insulin action, suggesting PC-1 as a therapeutic target for diabetes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Insulin resistance is linked to impaired insulin receptor tyrosine kinase activity, but gene mutations are rare.
  • Other molecules modulating insulin receptor function likely play a significant role in insulin resistance.
  • The function of membrane glycoprotein PC-1, a class II exoprotein, was previously unknown.

Purpose of the Study:

  • To identify molecules involved in insulin resistance.
  • To investigate the role of membrane glycoprotein PC-1 in insulin receptor function and insulin resistance.

Main Methods:

  • Cultured fibroblasts from insulin-resistant patients were used to identify PC-1.
  • PC-1 expression levels were analyzed in fibroblasts, muscle, and fat tissues.
  • PC-1 was transfected and expressed in cultured cells to assess its impact on insulin receptor activity and cellular responses.

Main Results:

  • Membrane glycoprotein PC-1 was identified as an inhibitor of insulin receptor tyrosine kinase activity.
  • PC-1 is overexpressed in insulin-resistant subjects and inversely correlated with insulin action in vivo and in vitro.
  • Overexpression of PC-1 in cultured cells impaired insulin receptor tyrosine kinase activity and insulin signaling.

Conclusions:

  • PC-1 is a significant factor in the etiology of insulin resistance.
  • PC-1 represents a potential therapeutic target for anti-diabetic therapies.

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