Plasma sulphur-containing amino acids and related metabolites are associated with insulin sensitivity, although the mechanisms are unclear. We examined the effect of exercise on this relationship. Dysglycemic (n = 13) and normoglycemic (n = 13) men underwent 45 min cycling before and after 12 weeks exercise intervention. We performed hyperinsulinemic euglycemic clamp, mRNA-sequencing of skeletal muscle and adipose tissue biopsies, and targeted profiling of plasma metabolites by LC-MS/MS. Insulin sensitivity increased similarly in dysglycemic and normoglycemic men after 12 weeks of exercise, in parallel to similar increases in concentration of plasma glutamine, and decreased concentrations of plasma glutamate, cysteine, taurine, and glutathione. Change in plasma concentrations of cysteine and glutathione exhibited the strongest correlations to exercise-improved insulin sensitivity, and expression of a cluster of genes essential for oxidative phosphorylation and fatty acid metabolism in both skeletal muscle and adipose tissue, as well as mitochondria-related genes such as mitofilin. Forty-five min of cycling decreased plasma concentrations of glutamine and methionine, and increased plasma concentrations of glutamate, homocysteine, cystathionine, cysteine, glutathione, and taurine. Similar acute responses were seen in both groups before and after the 12 weeks training period. Both acute and long-term exercise may influence transsulphuration and glutathione biosynthesis, linking exercise-improved insulin sensitivity to oxidative stress and mitochondrial function.
Keywords: amino acids; cysteine; exercise; glutathione; insulin sensitivity; prediabetes.