Elevated PC-1 content in cultured skin fibroblasts correlates with decreased in vivo and in vitro insulin action in nondiabetic subjects: evidence that PC-1 may be an intrinsic factor in impaired insulin receptor signaling.
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-1 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.
Frittitta
L
L
Institute of Internal Medicine, Endocrine and Metabolic Diseases, University of Catania, Garibaldi Hospital, Italy. segmeint@mbox.unict.it
Spampinato
D
D
Solini
A
A
Nosadini
R
R
Goldfine
I D
ID
Vigneri
R
R
Trischitta
V
V
D000328:Adult; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D005215:Fasting; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin
D007328:Insulin; D008562:Membrane Glycoproteins; D006003:Glycogen; D002784:Cholesterol; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D005947:Glucose