Effect of Exogenous Hydrogen Sulfide and Polysulfide Donors on Insulin Sensitivity of the Adipose Tissue

Hydrogen sulfide (H₂S) and inorganic polysulfides are important signaling molecules; however, little is known about their role in adipose tissue. We examined the effect of H₂S and polysulfides on insulin sensitivity of the adipose tissue in rats. Plasma glucose, insulin, non-esterified fatty acids, and glycerol were measured after administration of H₂S and the polysulfide donors, Na₂S and Na₂S₄, respectively. In addition, the effect of Na₂S and Na₂S₄ on insulin-induced glucose uptake and inhibition of lipolysis was studied in adipose tissue explants ex vivo. Na₂S and Na₂S₄ administered in vivo at a single dose of 100 μmol/kg had no effect on plasma glucose and insulin concentrations. In addition, Na₂S and Na₂S₄ did not modify the effect of insulin on plasma glucose, fatty acids, and glycerol concentrations. Na₂S and Na₂S₄had no effect on the antilipolytic effect of insulin in adipose tissue explants ex vivo. The effect of insulin on 2-deoxyglucose uptake by adipose tissue was impaired in obese rats which was accompanied by lower insulin-induced tyrosine phosphorylation of IRS-1 and Akt. Na₂S₄, but not Na₂S, improved insulin signaling and increased insulin-stimulated 2-deoxyglucose uptake by adipose tissue of obese rats. The results suggest that polysulfides may normalize insulin sensitivity, at least in the adipose tissue, in obesity/metabolic syndrome.