PC-1 content in skeletal muscle of non-obese, non-diabetic subjects: relationship to insulin receptor tyrosine kinase and whole body insulin sensitivity.
Insulin sensitivity varies widely in non-obese, non-diabetic subjects, and we have previously reported that in vivo insulin action correlates with in vitro insulin stimulated insulin receptor tyrosine-kinase activity in skeletal muscle. Plasma membrane glyco-protein PC-1 content is elevated in fibroblasts of insulin-resistant subjects, and expression of PC-1 cDNA in cultured cells reduces both insulin receptor tyrosine-kinase activity and the biological actions of insulin. In the present study we investigated non-obese, non-diabetic subjects and found a significant negative correlation between muscle PC-1 content and both in vivo insulin action as measured by the intravenous insulin tolerance test (r = -0.51, p = 0.035) and the sensitivity (ED50) of in vitro insulin stimulation of insulin receptor tyrosine-kinase activity (r = 0.66, p = 0.027). These studies indicate, therefore, that increased muscle PC-1 content is associated with reduced insulin action both in vivo and in vitro. Moreover, they suggest a possible role for PC-1 in regulating insulin receptor function in human skeletal muscle.
Frittitta
L
L
Istituto di Medicina Interna e Malattie Endocrine e Metaboliche, Università di Catania, Ospedale Garibaldi, Italy.
Youngren
J
J
Vigneri
R
R
Maddux
B A
BA
Trischitta
V
V
Goldfine
I D
ID
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases; D011972:Receptor, Insulin / Q000378:metabolism*; D012016:Reference Values; D012044:Regression Analysis
D001786:Blood Glucose; D007328:Insulin; D008562:Membrane Glycoproteins; D011972:Receptor, Insulin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases