INCREASED ADIPOSE-TISSUE PC-1 PROTEIN-CONTENT, BUT NOT TUMOR-NECROSIS-FACTOR-ALPHA GENE-EXPRESSION, IS ASSOCIATED WITH A REDUCTION OF BOTH WHOLE-BODY INSULIN SENSITIVITY AND INSULIN-RECEPTOR TYROSINE-KINASE ACTIVITY

In the present study we measured PC-1 content, tumour necrosis factor (TNF)-alpha gene expression, and insulin stimulation of insulin recept or tyrosine-kinase activity in adipose tissue from nonobese, non-diabe tic subjects. These parameters were correlated with in vivo insulin ac tion as measured by the intravenous insulin tolerance test (K-itt valu es). PC-1 content was negatively correlated with K-itt values (r = -0. 5, p = 0.04) and positively with plasma insulin levels both fasting (r = 0.58, p = 0.009) and after 120 min during oral glucose tolerance te st (OGTT) (r = 0.67, p = 0.002). Moreover, adipose tissue PC-1 content was higher in relatively insulin-resistant subjects (K-itt values low er than 6) than in relatively insulin-sensitive subjects (K-itt values higher than 6) (525+/-49 ng/mg protein vs 336+/-45, respectively, p = 0.012). Adipose tissue insulin receptor tyrosine-kinase activity in r esponse to insulin was significantly lower at all insulin concentratio ns tested (p = 0.017, by two-way analysis of variance test) in insulin -resistant than in insulin-sensitive subjects (K-itt values lower or h igher than 6, respectively). In contrast to PC-1, no significant corre lation was observed between adipose tissue TNF-alpha mRNA content and K-itt values, and plasma insulin levels, both fasting and at after 120 min during OGTT. Also, no difference was observed in TNF-alpha mRNA c ontent between subjects with K-itt values higher or lower than 6. Thes e studies in adipose tissue, together with our previous studies in ske letal muscle raise the possibility that PC-1, by regulating insulin re ceptor function, may play a role in the degree of insulin sensitivity in non-obese, non-diabetic subjects.