Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus

Nature. 1995 Feb 2;373(6513):448-51. doi: 10.1038/373448a0.


Most patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin. Insulin resistance precedes the onset of this disease, suggesting that it may be an initial abnormality. Insulin-receptor kinase activity is impaired in muscle, fibroblasts and other tissues of many patients with non-insulin-dependent diabetes mellitus, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase. Here we show that this inhibitor is a membrane glycoprotein, termed PC-1 (refs 10, 11). We find that PC-1 activity is increased in fibroblasts from seven of nine patients with typical non-insulin-dependent diabetes mellitus. In addition, overexpression of PC-1 in transfected cultured cells reduces insulin-stimulated tyrosine kinase activity. These studies raise the possibility that PC-1 has a role in the insulin resistance of non-insulin-dependent diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Insulin Resistance*
  • Male
  • Membrane Glycoproteins / isolation & purification
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Phosphoric Diester Hydrolases*
  • Pyrophosphatases*
  • Rats
  • Rats, Wistar
  • Receptor, Insulin / antagonists & inhibitors
  • Receptor, Insulin / metabolism*
  • Transfection
  • Tumor Cells, Cultured


  • Membrane Glycoproteins
  • Receptor, Insulin
  • Phosphoric Diester Hydrolases
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • Pyrophosphatases