Premium
Role of PC‐1 in The Etiology of Insulin Resistance
Author(s) -
GOLDFINE IRA D.,
MADDUX BETTY A.,
YOUNGREN JACK F.,
TRISCHITTA VINCENZO,
FRITTITTA LUCIA
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb07797.x
Subject(s) - insulin resistance , etiology , insulin , resistance (ecology) , chemistry , medicine , endocrinology , biology , ecology
Defects in insulin receptor tyrosine kinase activity have been demonstrated in tissues from insulin resistant subjects, but mutations in the insulin receptor gene are rare. Therefore, other molecules that are capable of modulating the insulin receptor most likely play a major role in insulin resistance. In cultured fibroblasts from an insulin resistant patient with Type 2 diabetes, we first identified membrane glycoprotein PC‐1 as an inhibitor of the insulin receptor tyrosine kinase activity. PC‐1 is overexpressed in fibroblasts from other insulin resistant subjects, both with and without Type 2 diabetes. PC‐1 is a large class II exoprotein whose function is unknown. Studies in muscle and fat of insulin resistant subjects, two primary tissues for insulin activation, reveal that elevated levels of PC‐1 are inversely correlated with decreased insulin action both in vivo and in vitro . Transfection and expression of PC‐1 in cultured cells demonstrate that overexpression of PC‐1 produces impairments in insulin receptor tyrosine kinase activity, and the subsequent cellular responses to insulin. These studies indicate, therefore, that PC‐1 is a major factor in the etiology of insulin resistance, and is a potential new therapeutic target for antidiabetic therapy.