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

Betty A. Maddux; Paolo Sbraccia; Shinobu Kumakura; Shlomo Sasson; Jack Youngren; Alexander Fisher; Steven Spencer; Andrew Grupe; William Henzel; Timothy A. Stewart; Gerald M. Reaven; Ira D. Goldfine

doi:10.1038/373448a0

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

Betty A. Maddux, Paolo Sbraccia, Shinobu Kumakura, Shlomo Sasson, Jack Youngren, Alexander Fisher, Steven Spencer, Andrew Grupe, William Henzel, Timothy A. Stewart, Gerald M. Reaven, Ira D. Goldfine^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

313 Scopus citations

Abstract

Most patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin¹. Insulin resistance precedes the onset of this disease^2-4, 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 mellitus⁵, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity^{6, 7}. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase^{8, 9}. 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.

Original language	English
Pages (from-to)	448-451
Number of pages	4
Journal	Nature
Volume	373
Issue number	6513
DOIs	https://doi.org/10.1038/373448a0
State	Published - 2 Feb 1995
Externally published	Yes

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title = "Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus",

abstract = "Most patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin1. Insulin resistance precedes the onset of this disease2-4, 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 mellitus5, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity6, 7. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase8, 9. 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.",

author = "Maddux, {Betty A.} and Paolo Sbraccia and Shinobu Kumakura and Shlomo Sasson and Jack Youngren and Alexander Fisher and Steven Spencer and Andrew Grupe and William Henzel and Stewart, {Timothy A.} and Reaven, {Gerald M.} and Goldfine, {Ira D.}",

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AU - Sbraccia, Paolo

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AU - Sasson, Shlomo

AU - Youngren, Jack

AU - Fisher, Alexander

AU - Spencer, Steven

AU - Grupe, Andrew

AU - Henzel, William

AU - Stewart, Timothy A.

AU - Reaven, Gerald M.

AU - Goldfine, Ira D.

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N2 - Most patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin1. Insulin resistance precedes the onset of this disease2-4, 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 mellitus5, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity6, 7. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase8, 9. 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.

AB - Most patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin1. Insulin resistance precedes the onset of this disease2-4, 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 mellitus5, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity6, 7. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase8, 9. 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.

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

Abstract

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