PC-1 CONTENT IN SKELETAL-MUSCLE OF NONOBESE, NONDIABETIC SUBJECTS - RELATIONSHIP TO INSULIN-RECEPTOR TYROSINE KINASE AND WHOLE-BODY INSULINSENSITIVITY

Insulin sensitivity varies widely in non-obese, non-diabetic subjects, and we have previously reported that in vivo insulin action correlate s with in vitro insulin stimulated insulin receptor tyrosine-kinase ac tivity in skeletal muscle. Plasma membrane glycoprotein PC-1 content i s elevated in fibroblasts of insulin-resistant subjects, and expressio n of PC-1 cDNA in cultured cells reduces both insulin receptor tyrosin e-kinase activity and the biological actions of insulin. In the presen t study we investigated non-obese, non-diabetic subjects and found a s ignificant: negative correlation between muscle PC-1 content and both in vivo insulin action as measured by the intravenous insulin toleranc e test (r = -0.51, p = 0.035) and the sensitivity (ED(50)) of in vitro insulin stimulation of insulin receptor tyrosine kinase activity (r = 0.66, p = 0.027). These studies indicate, therefore, that increased m uscle 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.