ArticleMolecular metabolism2015
The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pooled it
- Sitagliptin improves diastolic cardiac function but not cardiorespiratory fitness in adults with type 2 diabetes.Journal of diabetes and its complications · 2019Trial
- Exercise pills for cardiometabolic health cannot mimic the exercise milieu.Trends in endocrinology and metabolism: TEM · 2026Review
- Effect of metformin in a novel experimental model of peripheral artery disease.Clinical science (London, England : 1979) · 2025Article
- Health-related fitness benefits following concurrent high-intensity interval training and resistance training in patients with type-1 diabetes or type-2 diabetes.Frontiers in physiology · 2024Article
- PRMT5 links lipid metabolism to contractile function of skeletal muscles.EMBO reports · 2023Article
- Cellular and Molecular Regulation of Exercise-A Neuronal Perspective.Cellular and molecular neurobiology · 2023Review
- Natural (dihydro)phenanthrene plant compounds are direct activators of AMPK through its allosteric drug and metabolite-binding site.The Journal of biological chemistry · 2022Article
- Article
- Exercise mimetics: harnessing the therapeutic effects of physical activity.Nature reviews. Drug discovery · 2021Review
- Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats.Frontiers in endocrinology · 2021Article
- Reciprocity Between Skeletal Muscle AMPK Deletion and Insulin Action in Diet-Induced Obese Mice.Diabetes · 2020Article
- Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake.Comprehensive Physiology · 2020Review
- Excess Accumulation of Lipid Impairs Insulin Sensitivity in Skeletal Muscle.International journal of molecular sciences · 2020Review
- AMP-activated protein kinase: the current landscape for drug development.Nature reviews. Drug discovery · 2019Review
- PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients.JCI insight · 2018Article
- AMPK in skeletal muscle function and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Review
- AMPK: guardian of metabolism and mitochondrial homeostasis.Nature reviews. Molecular cell biology · 2018Review
- Exercise Mimetics: Impact on Health and Performance.Cell metabolism · 2017Review
- Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSkeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatment improves insulin sensitivity and exercise capacity in obese insulin resistant mice and whether skeletal muscle AMPK was important for mediating potential effects.
methodsGlucose homeostasis, insulin sensitivity, exercise capacity, and electron transport chain content/activity were examined in wildtype (WT) and AMPK β1β2 muscle-specific null (AMPK-MKO) mice fed a high-fat diet (HFD) with or without R419 supplementation.
resultsThere was no change in weight gain, adiposity, glucose tolerance or insulin sensitivity between HFD-fed WT and AMPK-MKO mice. In both HFD-fed WT and AMPK-MKO mice, R419 enhanced insulin tolerance, insulin-stimulated glucose disposal, skeletal muscle 2-deoxyglucose uptake, Akt phosphorylation and glucose transporter 4 (GLUT4) content independently of alterations in body mass. In WT, but not AMPK-MKO mice, R419 improved treadmill running capacity. Treatment with R419 increased muscle electron transport chain content and activity in WT mice; effects which were blunted in AMPK-MKO mice.
conclusionsTreatment of obese mice with R419 improved skeletal muscle insulin sensitivity through a mechanism that is independent of skeletal muscle AMPK. R419 also increases exercise capacity and improves mitochondrial function in obese WT mice; effects that are diminished in the absence of skeletal muscle AMPK. These findings suggest that R419 may be a promising therapy for improving whole-body glucose homeostasis and exercise capacity.
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Registered trials
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