Nonequilibrium thermodynamics and mitochondrial protein content predict insulin sensitivity and fuel selection during exercise in human skeletal muscle

被引:0
作者
Bustos, Rocio Zapata [1 ,2 ]
Coletta, Dawn K. [1 ,2 ,3 ]
Galons, Jean-Philippe [4 ]
Davidson, Lisa B. [1 ,2 ]
Langlais, Paul R. [1 ,2 ]
Funk, Janet L. [1 ]
Willis, Wayne T. [1 ,2 ]
Mandarino, Lawrence J. [1 ,2 ]
机构
[1] Univ Arizona, Dept Med, Div Endocrinol, Tucson, AZ 85721 USA
[2] Univ Arizona, Ctr Dispar Diabet Obes & Metab, Tucson, AZ 85721 USA
[3] Univ Arizona, Dept Physiol, Tucson, AZ USA
[4] Univ Arizona, Dept Med Imaging, Tucson, AZ USA
关键词
skeletal muscle; 31 P-magnetic resonance spectroscopy; mitochondria; exercise; insulin sensitivity; fuel selection; RESONANCE-BASED MEASUREMENTS; OXIDATIVE-PHOSPHORYLATION; GLUCOSE-METABOLISM; IN-VIVO; CARBOHYDRATE-METABOLISM; CREATINE-KINASE; LINEAR RELATION; ATP HYDROLYSIS; RESISTANCE; ENERGY;
D O I
10.3389/fphys.2023.1208186
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Introduction: Many investigators have attempted to define the molecular nature of changes responsible for insulin resistance in muscle, but a molecular approach may not consider the overall physiological context of muscle. Because the energetic state of ATP (& UDelta;G(ATP)) could affect the rate of insulin-stimulated, energy-consuming processes, the present study was undertaken to determine whether the thermodynamic state of skeletal muscle can partially explain insulin sensitivity and fuel selection independently of molecular changes.Methods: P-31-MRS was used with glucose clamps, exercise studies, muscle biopsies and proteomics to measure insulin sensitivity, thermodynamic variables, mitochondrial protein content, and aerobic capacity in 16 volunteers.Results: After showing calibrated P-31-MRS measurements conformed to a linear electrical circuit model of muscle nonequilibrium thermodynamics, we used these measurements in multiple stepwise regression against rates of insulin-stimulated glucose disposal and fuel oxidation. Multiple linear regression analyses showed 53% of the variance in insulin sensitivity was explained by 1) VO2max (p = 0.001) and the 2) slope of the relationship of & UDelta;G(ATP) with the rate of oxidative phosphorylation (p = 0.007). This slope represents conductance in the linear model (functional content of mitochondria). Mitochondrial protein content from proteomics was an independent predictor of fractional fat oxidation during mild exercise (R-2 = 0.55, p = 0.001).Conclusion: Higher mitochondrial functional content is related to the ability of skeletal muscle to maintain a greater & UDelta;G(ATP), which may lead to faster rates of insulin-stimulated processes. Mitochondrial protein content per se can explain fractional fat oxidation during mild exercise.
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页数:14
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