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Updated: Sep 6, 2025

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
AIFM2 Is Required for High-Intensity Aerobic Exercise in Promoting Glucose Utilization.
Hai P Nguyen1, Sneha Damal Villivalam2, Byung Chul Jung2
1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA.
Apoptosis-inducing mitochondrion-associated factor 2 (AIFM2) enhances exercise capacity by boosting glucose utilization in skeletal muscles. This protein is crucial for maintaining energy levels during physical activity.
Area of Science:
- Exercise physiology
- Cellular metabolism
- Molecular biology
Background:
- Skeletal muscle regulates blood sugar and dramatically increases glucose use during exercise.
- Efficient glycolysis requires adequate cytosolic NAD+ levels.
- Apoptosis-inducing mitochondrion-associated factor 2 (AIFM2) is known to promote glycolysis.
Purpose of the Study:
- To investigate the role of AIFM2 in skeletal muscle glucose metabolism and exercise performance.
- To determine if AIFM2 induction in specific muscles impacts exercise capacity.
Main Methods:
- Examined AIFM2 expression in extensor digitorum longus (EDL) muscle during exercise.
- Overexpressed AIFM2 in myotubes to assess its effect on NAD+/NADH ratio and glycolysis.
- Used in vivo methods (hairpin transfection, tamoxifen-inducible haploinsufficiency) to deplete AIFM2 in mouse muscles.
- Introduced Saccharomyces cerevisiae external NADH dehydrogenase (NDE1) in AIFM2-deficient mice.
Main Results:
- AIFM2 is highly induced in glycolytic EDL muscle during exercise.
- AIFM2 overexpression elevates NAD+/NADH ratio, increasing glycolytic rate and exercise capacity.
- Muscle-specific AIFM2 depletion reduces exercise capacity and glucose utilization.
- NDE1 introduction ameliorates exercise intolerance in AIFM2-haploinsufficient mice.
Conclusions:
- AIFM2 plays a critical role in regulating glucose utilization in glycolytic skeletal muscles.
- AIFM2 enhances exercise capacity by improving metabolic efficiency.
- AIFM2 is a novel target for improving skeletal muscle function and metabolic health.
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