Endocrine Abstracts

One of the key actions of insulin is the regulation of glucose and lipid oxidation. Disturbances in substrate oxidation play an important role in the development of insulin resistance. Insulin action is inversely associated with circulating pro-inflammatory cytokines such as soluble TNF-α receptors (sTNFR1 and sTNFR2).

The aim of the present study was to analyze the associations between serum sTNFR1 and sTNFR2 concentrations and glucose and lipid oxidation and non-oxidative glucose metabolism in lean and obese subjects with normal glucose tolerance.

We examined 42 subjects (30 females and 12 males), 22 lean (BMI<25 kg×m⁻², 16 females and 6 males) and 20 with overweight or obesity (BMI>25 kg×m⁻², 14 females and 6 males) with normal glucose tolerance. Insulin sensitivity was measured with the hyperinsulinemic euglycemic clamp technique. Glucose and lipid oxidation was evaluated with indirect calorimetry in the baseline state and during the last 30 min of the clamp. Non-oxidative glucose metabolism in the hyperinsulinemic state was calculated by subtracting glucose oxidation from the total glucose metabolism. Metabolic flexibility was assessed as an increase in respiratory quotient (ΔRQ) in response to insulin.

Serum sTNFR1 concentrations were higher in the obese in comparison with the lean group (P<0.0001). Insulin sensitivity was negatively related with serum sTNFR1 (r=−0.38, P=0.014), whereas the relationship with sTNFR2 was approaching the level of significance (r=−0.30, P=0.057). Serum sTNFR1 concentration was positively associated with the baseline glucose oxidation (r=0.32, P=0.043) and negatively – with the increase in glucose oxidation in response to insulin (r=−0.40, P=0.01) and with non-oxidative glucose metabolism (r=−0.35, P=0.022). Significant negative correlation between serum sTNFR1 and metabolic flexibility was observed (r=−0.36, P=0.019). Serum sTNFR2 was positively related to baseline respiratory quotient (r=0.36, P=0.018).

Our data suggest that TNFα system is associated with multiple metabolic pathways regulated by insulin.