APPS November 2002 Meeting Abstract 1220


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

Andrew L. Carey, Clinton R. Bruce, Mitchell J. Anderson, John A. Hawley, Mark A. Febbraio, School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia.

The effect of the cytokine interleukin (IL)-6 on insulin resistance is unclear. While a positive correlation between circulating IL-6 1 and/or adipose tissue IL-6 protein content 2 with obesity and insulin resistance is observed in humans, an IL-6 deficient mouse becomes overweight and glucose intolerant with advanced age 3. IL-6 is expressed in skeletal muscle but no studies have examined whether IL-6 expression in skeletal muscle is associated with insulin resistance. In the present study, the skeletal muscle expression and plasma concentrations of IL-6 were studies in type 2 diabetic patients (T2, n=11), age-matched non-diabetic subjects (AMC, n=6), and young healthy control subjects (YC, n=6). We hypothesised that neither skeletal muscle IL-6 nor circulating IL-6 would be an accurate predictor of insulin resistance in humans. 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. 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) in the final 30 minutes of CLAMP, corrected for lean body mass 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.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. These results demonstrate that there is an elevation in circulating plasma IL-6 concentration with age consistent with previous observations 4. However since T2 and AMC were BMI and age-matched, no differences were seen in plasma IL-6 or skeletal muscle IL-6 mRNA and no correlations were found between GDR and IL-6, our data clearly demonstrated that neither circulating IL-6 nor skeletal muscle IL-6 mRNA are predictors of insulin resistance in patients with type 2 diabetes.

(1) Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. American Journal of Physiology. 2001;280: E745-751.

(2) Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert J, Capeau J, Hainque B. Journal of Clinical and Endocrinological Metabolism. 2002;87:2084-2089.

(3) Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO. Nature Medicine. 2002;8:75-79

(4) Bruunsgaard H, Pedersen M, Pedersen BK. Current Opinion in Hematology. 2001;8:131-136.


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