Evidence map›Paper›PMID 41739941›Full record

ArticleScience advances2026

Ampk alpha2 T172 activation dictates exercise performance and energy transduction in skeletal muscle.

Ryan N Montalvo, Xiaolu Li, Gina M Many, Tyler J Sagendorf, Qing Yu, Wenqing Shen, Nishikant Wase, A Robert Burgardt, Tong Zhang, Marina A Gritsenko and 7 more

Abstract read
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Ryan N MontalvoCenter for Exercise Medicine Research, Fralin Biomedical Research Institute at the Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA.ORCID 0000-0002-0323-4545
Xiaolu LiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.ORCID 0000-0002-9845-1584
Gina M ManyBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.ORCID 0000-0003-4779-1690
Tyler J SagendorfBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.ORCID 0000-0003-1552-4870
Qing YuCenter for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
Wenqing ShenCenter for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
Nishikant WasePPD, Thermo Fisher Scientific, Richmond, VA, 23229, USA.ORCID 0000-0002-8955-3300
A Robert BurgardtCenter for Exercise Medicine Research, Fralin Biomedical Research Institute at the Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA.ORCID 0009-0001-9551-0921
Tong ZhangBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.ORCID 0000-0003-2540-2017
Marina A GritsenkoBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.ORCID 0000-0001-9992-9829
Matthew J GaffreyBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.ORCID 0009-0001-2436-6969
Hemangi BhonsleCenter for Exercise Medicine Research, Fralin Biomedical Research Institute at the Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA.
Yuntian GuanCenter for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.ORCID 0000-0003-0809-768X
Xuansong MaoCenter for Exercise Medicine Research, Fralin Biomedical Research Institute at the Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA.
Mei ZhangCenter for Exercise Medicine Research, Fralin Biomedical Research Institute at the Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA.ORCID 0009-0006-3374-995X
Wei-Jun QianBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.ORCID 0000-0002-5393-2827
Zhen YanCenter for Exercise Medicine Research, Fralin Biomedical Research Institute at the Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA.ORCID 0000-0002-4826-9813

Funding

p38 MAPK a regulator of muscle contraction and functionR01AR050429 · NIAMS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI YAN, ZHEN · 2005 to 2022
$5.3M
mitoAMPK in exercise benefitsR01AR077440 · NIAMS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI YAN, ZHEN · 2020 to 2024
$2.1M
NIAMS NIH HHS R01 AR050429NIAMS NIH HHS R01 AR077440
6 · The paper itself

Abstract

Adenosine 5'-monophosphate-activated protein kinase (AMPK) is an energetic sensor for metabolic regulation and integration. Here, we used CRISPR-Cas9 to generate nonactivatable Ampkα knock-in (KI) mice with mutation of threonine-172 phosphorylation site to alanine (T172A), circumventing the limitations of previous genetic interventions that disrupt the protein stoichiometry. KI mice of Ampkα2, but not Ampkα1, demonstrated phenotypic changes with increased fat-to-lean mass, impaired endurance exercise capacity, and diminished mitochondrial maximal respiration and conductance in skeletal muscle. Integrated temporal multiomics analysis (proteomics/phosphoproteomics/metabolomics) in skeletal muscle at rest and during exercise establishes a pleiotropic yet imperative role of Ampkα2 T172 activation for glycolytic and oxidative metabolism, mitochondrial respiration, and contractile function. There is a substantial overlap of skeletal muscle proteomic changes in Ampkα2 T172A KI mice with that of patients with type 2 diabetes. Our findings suggest that Ampkα2 T172 activation is critical for exercise performance and energy transduction in skeletal muscle and may serve as a therapeutic target for type 2 diabetes.

Indexed as

AMP-Activated Protein KinasesEnergy MetabolismMuscle, SkeletalPhysical Conditioning, AnimalAnimalsDiabetes Mellitus, Type 2Enzyme ActivationGene Knock-In TechniquesHumansMicePhosphorylationProteomicsSignal TransductionAMP-Activated Protein KinasesPrkaa2 protein, mouse

Identifiers

PMID41739941
PMCPMC12935046

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.