Systemic effect of insulin on local cytokine concentrations in adipose tissue and muscle in healthy humans
Julia K Mader, Dimas Ikeoka, Heinz Weinhandl, Christoph Pachler, Gerlies Bock, Johannes Plank, Martin Ellmerer & Thomas R Pieber
Introduction: Cytokines are produced in different tissues under physiological and pathophysiological conditions. The present study was performed to compare local concentrations of cytokines in subcutaneous adipose tissue and muscle using the open flow microperfusion (OFM) technique, as well as to investigate systemic effects of insulin on interstitial concentrations of these mediators.
Methods: Ten healthy volunteers (age: 27±4 years, BMI: 22.6±1.6 kg/m2) underwent hyperinsulinemiceuglycemic clamp (HEC) and saline control experiments in a cross-over design. HEC was performed using primed continuous infusion of insulin at a constant rate (1.2 mU/kg per min) at variable glucose infusion, aiming to maintain blood glucose at basal levels. In each volunteer, two 18 gauge OFM catheters were inserted into abdominal subcutaneous adipose tissue (SAT) and rectus femoris muscle tissue, respectively. Both OFM catheters were perfused with manitol solution at constant flow rate of 1 μl/min. Effluent samples were collected in microvials on ice and frozen at −20 °C. For each study visit, pooled samples were analyzed for the concentrations of TNF-α, IL-6, IL-10, MCP-1, adiponectin, leptin and C-reactive protein using multiplexed ELISA assays.
Results: Plasma glucose concentrations were comparable between experiments (91±2 vs 88±2 mg/dl; HEC versus saline). Expectedly, leptin concentrations were significantly higher in SAT (1.2±1.6) versus muscle (0.3±0.4) tissue. No significant differences were observed when comparing HEC versus saline experiments.
Discussion: The results indicate that cytokines can be measured in SAT as well as in muscle of healthy volunteers using OFM. The higher activation of leptin gene in SAT might be the explanation for the observed difference of leptin between tissue sites. No clear pro- or anti-inflammatory effect of insulin on cytokine expression in peripheral tissues was observed.