Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males
Abstract
Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically matched aerobic exercise during acute (13C]glucose and [6,6-2H2]glucose). Metabolite profiles were analyzed in serum as change (Δ), calculated by subtracting postprandial/exercised state SL (ΔSL) and HA (ΔHA) from fasted, rested conditions at SL. Compared with SL, exogenous glucose oxidation, glucose rate of disappearance, and glucose metabolic clearance rate (MCR) were lower ( P < 0.05) during exercise at HA. One hundred and eighteen metabolites differed between ΔSL and ΔHA ( P < 0.05, Q < 0.10). Differences in metabolites indicated increased glycolysis, tricarboxylic acid cycle, amino acid catabolism, oxidative stress, and fatty acid storage, and decreased fatty acid mobilization for ΔHA. Branched-chain amino acids and oxidative stress metabolites, Δ3-methyl-2-oxobutyrate ( r = −0.738) and Δγ-glutamylalanine ( r = −0.810), were inversely associated ( P < 0.05) with Δexogenous glucose oxidation. Δ3-Hydroxyisobutyrate ( r = −0.762) and Δ2-hydroxybutyrate/2-hydroxyisobutyrate ( r = −0.738) were inversely associated ( P < 0.05) with glucose MCR. Coupling global metabolomics and glucose kinetic data suggest that the underlying cause for diminished exogenous glucose oxidative capacity during aerobic exercise is acute hypoxia-mediated peripheral insulin resistance.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 01, 2021
- Source ID
- 10.1152/ajpregu.00076.2021
Entities
People
- Andrew J Young
- Arny A. Ferrando
- J Philip Karl
- Julie L. Coleman
- Lee M. Margolis
- Marques A. Wilson
- Stefan M. Pasiakos
Organizations
- Oak Ridge Institute for Science and Education
- United States Army Research Institute of Environmental Medicine
- United States Department of Energy
- University of Arkansas for Medical Sciences