ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Combining metformin and aerobic exercise training in the treatment of type 2 diabetes and NAFLD in OLETF rats.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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.
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Who cites it
45 citing papers in PubMed, 79 citations in OpenAlex.
- Exercise-Induced Hepatic Mitochondrial Reprogramming Across Muscle-Gut-Thyroid Axes in MASLD/MASH.International journal of molecular sciences · 2026Review
- Hepatic ketogenesis is not required for exercise training to mitigate diet-induced liver steatosis in male mice.Function (Oxford, England) · 2026Article
- Restoring Mitochondrial Homeostasis: Therapeutic Strategies for Metabolic Dysfunction-Associated Fatty Liver Disease.International journal of molecular sciences · 2026Review
- Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides.Nutrients · 2025Review
- The Influence of Physical Exercise, Ketogenic Diet, and Time-Restricted Eating on De Novo Lipogenesis: A Narrative Review.Nutrients · 2025Review
- Mechanisms underpinning the effect of exercise on the non-alcoholic fatty liver disease: review.EXCLI journal · 2025Review
- Dual modulation of atherosclerosis by exercise and metformin: convergent pathways, divergent outcomes, and therapeutic potential.Clinical hypertension · 2025Review
- Review
- Clinical Considerations and Practical Advice for People Living With Type 2 Diabetes Who Undertake Regular Exercise or Aim to Exercise Competitively.Diabetes spectrum : a publication of the American Diabetes Association · 2023Article
- Exercise and inactivity as modifiers of β cell function and type 2 diabetes risk.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Review
- Physical activity is inversely associated with hepatic fibro-inflammation: A population-based cohort study using UK Biobank data.JHEP reports : innovation in hepatology · 2023Article
- Glucose-lowering effects of orally administered superoxide dismutase in type 2 diabetic model rats.NPJ science of food · 2022Article
- The Coexistence of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.Journal of clinical medicine · 2022Review
- Effects of High-Intensity Interval Training Protocols on Liver Enzymes and Wellness in Women.Journal of sports medicine (Hindawi Publishing Corporation) · 2021Article
- Exercise-Pharmacology Interactions: Metformin, Statins, and Healthspan.Physiology (Bethesda, Md.) · 2020Review
- DPP-4 inhibition resembles exercise in preventing type 2 diabetes development by inhibiting hepatic protein kinase CThe Journal of international medical research · 2020Article
- Physical exercise and liver "fitness": Role of mitochondrial function and epigenetics-related mechanisms in non-alcoholic fatty liver disease.Molecular metabolism · 2020Review
- Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways.Mediators of inflammation · 2020Review
- Metformin May Contribute to Inter-individual Variability for Glycemic Responses to Exercise.Frontiers in endocrinology · 2020Review
- Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Here, we sought to compare the efficacy of combining exercise and metformin for the treatment of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) in hyperphagic, obese, type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats (age: 20 wk, hyperglycemic and hyperinsulinemic; n = 10/group) were randomly assigned to sedentary (O-SED), SED plus metformin (O-SED + M; 300 mg·kg(-1)·day(-1)), moderate-intensity exercise training (O-EndEx; 20 m/min, 60 min/day, 5 days/wk treadmill running), or O-EndEx + M groups for 12 wk. Long-Evans Tokushima Otsuka (L-SED) rats served as nonhyperphagic controls. O-SED + M, O-EndEx, and O-EndEx + M were effective in the management of type 2 diabetes, and all three treatments lowered hepatic steatosis and serum markers of liver injury; however, O-EndEx lowered liver triglyceride content and fasting hyperglycemia more than O-SED + M. In addition, exercise elicited greater improvements compared with metformin alone on postchallenge glycemic control, liver diacylglycerol content, hepatic mitochondrial palmitate oxidation, citrate synthase, and β-HAD activities and in the attenuation of markers of hepatic fatty acid uptake and de novo fatty acid synthesis. Surprisingly, combining metformin and aerobic exercise training offered little added benefit to these outcomes, and in fact, metformin actually blunted exercise-induced increases in complete mitochondrial palmitate oxidation and β-HAD activity. In conclusion, aerobic exercise training was more effective than metformin administration in the management of type 2 diabetes and NAFLD outcomes in obese hyperphagic OLETF rats. Combining therapies offered little additional benefit beyond exercise alone, and findings suggest that metformin potentially impairs exercise-induced hepatic mitochondrial adaptations.
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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 Socratic graph.