TY - JOUR
T1 - Elevated PC-1 content in cultured skin fibroblasts correlates with decreased in vivo and in vitro insulin action in nondiabetic subjects
T2 - Evidence that PC-1 may be an intrinsic factor in impaired insulin receptor signaling
AU - Frittitta, Lucia
AU - Spampinato, Daniela
AU - Solini, Anna
AU - Nosadini, Romano
AU - Goldfine, Ira D.
AU - Vigneri, Riccardo
AU - Trischitta, Vincenzo
PY - 1998
Y1 - 1998
N2 - Membrane glycoprotein PC-1 inhibits insulin receptor (IR) tyrosine kinase activity and subsequent cellular signaling. PC-1 content is elevated in muscle and adipose tissue from insulin-resistant subjects, and its elevation correlates with in vivo insulin resistance. To determine whether elevated PC-I content is a primary cause of insulin resistance, we have now measured PC-1 content in cultured skin fibroblasts from nonobese nondiabetic insulin-resistant subjects and found that 1) PC-1 content was significantly higher in these cells when compared with cells from insulin-sensitive subjects (6.7 ± 0.9 vs. 3.1 ± 0.6 ng/0.1 mg protein, mean ± SE, P <0.01); 2) PC-1 content in fibroblasts was highly correlated with PC-1 content in muscle tissue (r = 0.95, P = 0.01); 3) PC-1 content in fibroblasts negatively correlated with both decreased in vivo insulin sensitivity and decreased in vitro IR autophosphorylation; and 4) in cells from insulin-resistant subjects, insulin stimulation of glycogen synthetase was decreased. These studies indicate, therefore, that the elevation of PC-1 content may be a primary factor in the cause of insulin resistance.
AB - Membrane glycoprotein PC-1 inhibits insulin receptor (IR) tyrosine kinase activity and subsequent cellular signaling. PC-1 content is elevated in muscle and adipose tissue from insulin-resistant subjects, and its elevation correlates with in vivo insulin resistance. To determine whether elevated PC-I content is a primary cause of insulin resistance, we have now measured PC-1 content in cultured skin fibroblasts from nonobese nondiabetic insulin-resistant subjects and found that 1) PC-1 content was significantly higher in these cells when compared with cells from insulin-sensitive subjects (6.7 ± 0.9 vs. 3.1 ± 0.6 ng/0.1 mg protein, mean ± SE, P <0.01); 2) PC-1 content in fibroblasts was highly correlated with PC-1 content in muscle tissue (r = 0.95, P = 0.01); 3) PC-1 content in fibroblasts negatively correlated with both decreased in vivo insulin sensitivity and decreased in vitro IR autophosphorylation; and 4) in cells from insulin-resistant subjects, insulin stimulation of glycogen synthetase was decreased. These studies indicate, therefore, that the elevation of PC-1 content may be a primary factor in the cause of insulin resistance.
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U2 - 10.2337/diabetes.47.7.1095
DO - 10.2337/diabetes.47.7.1095
M3 - Article
C2 - 9648833
AN - SCOPUS:0031747108
VL - 47
SP - 1095
EP - 1100
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -