A soluble PC-1 circulates in human plasma: Relationship with insulin resistance and associated abnormalities

An increased tissue content of PC-1, an inhibitor of insulin receptor signa ling, may play a role in insulin resistance. Large scale prospective studie s to test this hypothesis are difficult to carry out because of the need fo r tissue biopsies. The aim of this study was to investigate whether PC-1 is measurable in human plasma and whether its concentration is related to ins ulin sensitivity. A soluble PC-1, with mol wt and enzymatic activity similar to those of tiss ue PC-1, was measurable in human plasma by a specific enzyme-linked immunos orbent assay and was inversely correlated to skeletal muscle PC-1 content ( r = -0.5; P < 0.01). The plasma PC-1 concentration was decreased (P < 0.05) in insulin-resistant (22.7 +/- 3.0 ng/mL; n = 25) compared to insulin-sens itive (36.7 +/- 4.5; n = 25) nondiabetic subjects and was correlated negati vely with the waist/hip ratio (r = -0.48; P < 0.001) and mean blood pressur e (r = -0.3; P < 0.05) and positively with high density lipoprotein/total c holesterol (r = 0.38; P < 0.01) and both the M value and the plasma free fa tty acid level decrement at clamp studies (r = 0.28; n = 50; P = 0.05 and r = 0.43; n = 22; P < 0.05, respectively). A plasma PC-1 concentration of 19 ng/mL or less identified a cluster of insulin resistance-related alteratio ns with 75% accuracy. In conclusion, PC-1 circulates in human plasma, and its concentration is re lated to insulin sensitivity. This may help to plan studies aimed at unders tanding the role of PC-1 in insulin resistance.