Use of skeletal muscle fiber composition to assess relationship between amino acid metabolism and insulin sensitivity

Abstract Objective Here we use skeletal muscle fiber composition to investigate whether defects in amino acid metabolism are involved in the early development of IR in healthy young individuals before onset of clinical manifestations. Design Two groups consisting of healthy young men and women, insulin-sensitive and insulin resistant, were studied using a cross-sectional design. Methods Biopsies were obtained from the vastus lateralis muscle and an intravenous glucose tolerance test was performed. Plasma and muscle tissue were analyzed by metabolomics. Results Subjects in group 1 (n=20; age 28±5 yrs; body mass index 22.3±2.7 kg/m2) had an expression of type I muscle fibers and whole-body insulin sensitivity, respectively, of 58.8±5.7% and 1.8±0.7 units. Subjects in group 2 (n=16; age 25±6 yrs; body mass index 22.6±3.0 kg/m2) had an expression of type I muscle fibers and whole-body insulin sensitivity, respectively, of 29.8±6.6% and 0.8±0.3 units (P0.001 vs. group 1 for both). Anserine and β-alanine contents in muscle were significantly higher and taurine lower in group 2 vs. 1, consistent with the differences in muscle fiber composition between groups. Taurine correlated well with insulin sensitivity and expression of type I muscle fibers (r=0.63; P0.001 for both). In contrast, there were no significant differences in plasma or tissue contents of glutamine, arginine, or branch-chain amino acids between groups. Conclusions These data demonstrate that the early development of IR is not a consequence of defects in amino acid metabolism. Rather, defects in amino acid metabolism in diseased states are more likely a consequence of IR.