ArticleMolecular metabolism2021
Compound- and fiber type-selective requirement of AMPKγ3 for insulin-independent glucose uptake in skeletal muscle.
Article in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
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.
Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Activation of AMPK as a therapeutic strategy for FBXL4-related mitochondrial DNA depletion syndrome.EMBO molecular medicine · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- Protocol for muscle fiber type and cross-sectional area analysis in cryosections of whole lower mouse hindlimbs.bioRxiv : the preprint server for biology · 2024Article
- Fine-tuning AMPK in physiology and disease using point-mutant mouse models.Disease models & mechanisms · 2024Review
- AMPKγ3 Controls Muscle Glucose Uptake in Recovery From Exercise to Recapture Energy Stores.Diabetes · 2023Article
- New insights into activation and function of the AMPK.Nature reviews. Molecular cell biology · 2023Review
- Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1.Frontiers in pharmacology · 2023Article
- Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator.The Biochemical journal · 2022Article
- Natural (dihydro)phenanthrene plant compounds are direct activators of AMPK through its allosteric drug and metabolite-binding site.The Journal of biological chemistry · 2022Article
- Rhein for treating diabetes mellitus: A pharmacological and mechanistic overview.Frontiers in pharmacology · 2022Review
- Prior AICAR induces elevated glucose uptake concomitant with greater γ3-AMPK activation and reduced membrane cholesterol in skeletal muscle from 26-month-old rats.Facets (Ottawa) · 2022Article
- Direct small molecule ADaM-site AMPK activators reveal an AMPKγ3-independent mechanism for blood glucose lowering.Molecular metabolism · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 12 institutions in 6 countries.
Funding
Abstract
objectiveThe metabolic master-switch AMP-activated protein kinase (AMPK) mediates insulin-independent glucose uptake in muscle and regulates the metabolic activity of brown and beige adipose tissue (BAT). The regulatory AMPKγ3 isoform is uniquely expressed in skeletal muscle and potentially in BAT. Herein, we investigated the role that AMPKγ3 plays in mediating skeletal muscle glucose uptake and whole-body glucose clearance in response to small-molecule activators that act on AMPK via distinct mechanisms. We also assessed whether γ3 plays a role in adipose thermogenesis and browning.
methodsGlobal AMPKγ3 knockout (KO) mice were generated. A systematic whole-body, tissue, and molecular phenotyping linked to glucose homeostasis was performed in γ3 KO and wild-type (WT) mice. Glucose uptake in glycolytic and oxidative skeletal muscle ex vivo as well as blood glucose clearance in response to small molecule AMPK activators that target the nucleotide-binding domain of the γ subunit (AICAR) and allosteric drug and metabolite (ADaM) site located at the interface of the α and β subunit (991, MK-8722) were assessed. Oxygen consumption, thermography, and molecular phenotyping with a β3-adrenergic receptor agonist (CL-316,243) treatment were performed to assess BAT thermogenesis, characteristics, and function.
resultsGenetic ablation of γ3 did not affect body weight, body composition, physical activity, and parameters associated with glucose homeostasis under chow or high-fat diet. γ3 deficiency had no effect on fiber-type composition, mitochondrial content and components, or insulin-stimulated glucose uptake in skeletal muscle. Glycolytic muscles in γ3 KO mice showed a partial loss of AMPKα2 activity, which was associated with reduced levels of AMPKα2 and β2 subunit isoforms. Notably, γ3 deficiency resulted in a selective loss of AICAR-, but not MK-8722-induced blood glucose-lowering in vivo and glucose uptake specifically in glycolytic muscle ex vivo. We detected γ3 in BAT and found that it preferentially interacts with α2 and β2. We observed no differences in oxygen consumption, thermogenesis, morphology of BAT and inguinal white adipose tissue (iWAT), or markers of BAT activity between WT and γ3 KO mice.
conclusionsThese results demonstrate that γ3 plays a key role in mediating AICAR- but not ADaM site binding drug-stimulated blood glucose clearance and glucose uptake specifically in glycolytic skeletal muscle. We also showed that γ3 is dispensable for β3-adrenergic receptor agonist-induced thermogenesis and browning of iWAT.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.