Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus.
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.
Maddux
B A
BA
Division of Diabetes and Endocrine Research, Mount Zion Medical Center of the University of California, San Francisco 94115.
Sbraccia
P
P
Kumakura
S
S
Sasson
S
S
Youngren
J
J
Fisher
A
A
Spencer
S
S
Grupe
A
A
Henzel
W
W
Stewart
T A
TA
D000328:Adult; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D011972:Receptor, Insulin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases