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A Soluble PC-1 Circulates in Human Plasma: Relationship with Insulin Resistance and Associated Abnormalities¹

Istituto di Medicina Interna, Malattie Endocrine e Metaboliche, Università di Catania, Ospedale Garibaldi (L.F., R.B., B.C., S.G., D.S., R.V., V.T.), 95123 Catania; Consiglionazionale della Ricerca, Institute of Clinical Physiology and Department of Internal Medicine, University of Pisa (S.C., E.F.), 56100 Pisa; Divisione ed Unita di Ricerca di Endocrinologia, Istituto Scientifico Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo (V.T.), 71013 Foggia; and Divisione di Endocrinologia 1, Università La Sapienza (M.D.), 00100 Rome, Italy; and the Diabetes Research Laboratory, Mount Zion Hospital, University of California–San Francisco (M.D., B.A.M.), San Francisco, California 94143-1616

Address all correspondence and requests for reprints to: Lucia Frittitta, M.D., Endocrinologia, Ospedale Garibaldi, P.zza S. M. di Gesù, 95123 Catania, Italy. E-mail: segmeint{at}mbox.unict.it

An increased tissue content of PC-1, an inhibitor of insulin receptor signaling, may play a role in insulin resistance. Large scale prospective studies to test this hypothesis are difficult to carry out because of the need for 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 insulin sensitivity.

A soluble PC-1, with mol wt and enzymatic activity similar to those of tissue PC-1, was measurable in human plasma by a specific enzyme-linked immunosorbent 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-sensitive (36.7 ± 4.5; n = 25) nondiabetic subjects and was correlated negatively with the waist/hip ratio (r = -0.48; P < 0.001) and mean blood pressure (r = -0.3; P < 0.05) and positively with high density lipoprotein/total cholesterol (r = 0.38; P < 0.01) and both the M value and the plasma free fatty 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 alterations with 75% accuracy.

In conclusion, PC-1 circulates in human plasma, and its concentration is related to insulin sensitivity. This may help to plan studies aimed at understanding the role of PC-1 in insulin resistance.

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