Endocrine Abstracts

Introduction: Glycoprotein 130 (gp130) cytokines, like interleukin 6 (IL6), act through plasma membrane receptors consisting of two glycoproteins: a cytokine binding subunit (like IL6R) and gp130, responsible for signal transduction. IL6 may regulate insulin sensitivity in a dual manner, as both insulin-sensitizing and -desensitizing actions have been reported. Other gp130 cytokines may have a beneficial metabolic effects. The aim of the present study was to assess skeletal muscle and adipose tissue IL6R and gp130 expression in relation to insulin sensitivity and obesity in male subjects.

Methods: We examined 86 young (age 23.22±2.41 years), apparently healthy male subjects with normal glucose tolerance, 45 lean (BMI below 25 kg/m²) and 41 with overweight or obesity (BMI between 25 and 40 kg/m²). Euglycemic hyperinsulinemic clamp, indirect calorimetry and biopsies of vastus lateralis muscle and subcutaneous adipose tissue were performed. Tissue mRNA expression of IL6R, gp130, suppressor of cytokine signaling 3 (SOCS3), AMP-activated protein kinase (AMPK), and nuclear factor κ B (NFκB) was analyzed with real-time PCR.

Results: Obese subjects had higher adipose tissue gp130 expression (p=0.008). No difference in tissue IL6R was found. Both muscle and adipose tissue gp130 expression was inversely related to insulin sensitivity (r=−0.32, P=0.004 and r=−0.28, P=0.035, respectively). Only adipose tissue gp130 was related to its serum soluble form (r=0.34, P=0.01). Muscle gp130 was related to lipid oxidation during the clamp (r=0.24, P=0.035) and muscle AMPK (r=0.48, P=0.042). Adipose tissue gp130 was associated with adipose tissue SOCS3 (r=0.60, P=0.007) and NFκB expression (r=0.49, P=0.035).

Conclusions: Our data show that both muscle and adipose tissue gp130 expression is inversely related to insulin action. This association may be linked to lipid oxidation in muscle and inflammation in adipose tissue.