NEITHER CIRCULATING IL-6 NOR SKELETAL MUSCLE IL-6 mRNA ARE PREDICTORS OF INSULIN RESISTANCE IN HUMANS

Abstract

The effect of interleukin (IL)-6 on insulin resistance is unclear and while IL-6 is expressed in skeletal muscle, no studies have examined whether IL-6 expression in skeletal muscle is associated with insulin resistance. PURPOSE To determine whether insulin stimulates IL-6 production and whether IL-6 is associated with insulin resistance. METHODS Skeletal muscle mRNA expression and plasma concentrations of IL-6 were studies in type 2 diabetic patients (T2, n = 11), age-matched non-diabetic controls (AMC, n = 6), and young healthy subjects (YC, n = 6). Each subject underwent a euglycemic-hyperinsulinemic clamp (CLAMP) for 120 min. Muscle biopsies were obtained before and at cessation of CLAMP, and venous blood samples were obtained every 30 min. RESULTS No differences were observed in plasma IL-6 or intramuscular IL-6 mRNA when comparing pre- with post-CLAMP in any group. There was no difference in BMI between T2 and AMC (p > 0.05) but both had a higher (p < 0.05) BMI compared with YC. Glucose disposal rate (GDR) during CLAMP was higher in YC than AMC, both of whom had a higher GDR compared with T2 (17.6 ± 1.1, 10.7 ± 1.4, 3.3 ± 0.6 mg.kg−1.min−1 respectively; mean ± SE, p < 0.05). No differences were found between any groups for skeletal muscle IL-6 mRNA, either under basal conditions or immediately post-CLAMP. Plasma IL-6 concentrations were not different between T2 or AMC at any time point throughout CLAMP (p > 0.05), however both had higher (p < 0.05) plasma IL-6 concentrations throughout CLAMP compared with YC. No significant correlations were found between GDR and plasma IL-6 or skeletal muscle IL-6 mRNA in any group, but a positive correlation (r2 = 0.65; p < 0.05) was observed between basal plasma IL-6 and BMI. CONCLUSION Neither circulating plasma IL-6 nor IL-6 mRNA are stimulated by insulin. Circulating IL-6 concentration increases with age and is positively correlated with BMI, however our data demonstrated that neither circulating IL-6 nor skeletal muscle IL-6 mRNA are predictors of insulin resistance in patients with type 2 diabetes.