ArticleDiabetologia2023
Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice.
Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals.Science advances · 2025Trial
- CIDEB and CGI-58 differentially regulate liver lipid-droplet cholesterol to modulate metabolic dysfunction-associated steatohepatitis severity.Cell reports · 2026Article
- Hypothesis: Nutrient Off-Loading and Ectopic Fat Reduction Reverse Insulin Resistance and Improve Cardiovascular Outcomes in Type 2 Diabetes-A Narrative Review.International journal of molecular sciences · 2026Review
- Organelle-specific lipid profiles influence/underlie metabolic health in a nutrition-dependent manner.bioRxiv : the preprint server for biology · 2025Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: Myocellular mechanisms involved.Reviews in endocrine & metabolic disorders · 2025Review
- The Pivotal Role of the Western Diet, Hyperinsulinemia, Ectopic Fat, and Diacylglycerol-Mediated Insulin Resistance in Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Animal Models of Exercise and Cardiometabolic Disease.Circulation research · 2025Review
- Predicting Sprint Potential: A Machine Learning Model Based on Blood Metabolite Profiles in Young Male Athletes.European journal of sport science · 2025Article
- Diet-induced impairment of skeletal muscle and adipose tissue metabolic homeostasis and its prevention by probiotic administration.Pflugers Archiv : European journal of physiology · 2025Article
- Lipidomics and temporal-spatial distribution of organelle lipid.Journal of biological methods · 2025Review
- Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People With Obesity and Type 2 Diabetes.Diabetes · 2024Article
- Small molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease.American journal of physiology. Endocrinology and metabolism · 2024Article
- Article
- Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies.Drug design, development and therapy · 2024Review
- Article
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
aims/hypothesisAthletes exhibit increased muscle insulin sensitivity, despite increased intramuscular triacylglycerol content. This phenomenon has been coined the 'athlete's paradox' and is poorly understood. Recent findings suggest that the subcellular distribution of sn-1,2-diacylglycerols (DAGs) in the plasma membrane leading to activation of novel protein kinase Cs (PKCs) is a crucial pathway to inducing insulin resistance. Here, we hypothesised that regular aerobic exercise would preserve muscle insulin sensitivity by preventing increases in plasma membrane sn-1,2-DAGs and activation of PKCε and PKCθ despite promoting increases in muscle triacylglycerol content.
methodsC57BL/6J mice were allocated to three groups (regular chow feeding [RC]; high-fat diet feeding [HFD]; RC feeding and running wheel exercise [RC-EXE]). We used a novel LC-MS/MS/cellular fractionation method to assess DAG stereoisomers in five subcellular compartments (plasma membrane [PM], endoplasmic reticulum, mitochondria, lipid droplets and cytosol) in the skeletal muscle.
resultsWe found that the HFD group had a greater content of sn-DAGs and ceramides in multiple subcellular compartments compared with the RC mice, which was associated with an increase in PKCε and PKCθ translocation. However, the RC-EXE mice showed, of particular note, a reduction in PM sn-1,2-DAG and ceramide content when compared with HFD mice. Consistent with the PM sn-1,2-DAG-novel PKC hypothesis, we observed an increase in phosphorylation of threonine CONCLUSIONS/
interpretationThese results demonstrate that lower PKCθ/PKCε activity and sn-1,2-DAG content, especially in the PM compartment, can explain the preserved muscle insulin sensitivity in RC-EXE mice.
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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.