ArticleThe Journal of physiology2010
Acute exercise reduces hepatic glucose production through inhibition of the Foxo1/HNF-4alpha pathway in insulin resistant mice.
Article in The Journal of physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Critical role of AKT protein in myeloma-induced osteoclast formation and osteolysis.The Journal of biological chemistry · 2013Trial
- Berberine: A Rising Star in the Management of Type 2 Diabetes-Novel Insights into Its Anti-Inflammatory, Metabolic, and Epigenetic Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Analysis of ROH Characteristics Across Generations in Grassland-Thoroughbred Horses and Identification of Loci Associated with Athletic Traits.Animals : an open access journal from MDPI · 2025Article
- HM-Chromanone Alleviates Hyperglycemia by Activating AMPK and PI3K/AKT Pathways in Mice Fed a High-Fat Diet.Nutrients · 2024Article
- Article
- Exercise and inactivity as modifiers of β cell function and type 2 diabetes risk.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Review
- Labeled breath tests in patients with NASH: Octanoate oxidation relates best to measures of glucose metabolism.Frontiers in physiology · 2023Article
- HIIT Ameliorates Inflammation and Lipid Metabolism by Regulating Macrophage Polarization and Mitochondrial Dynamics in the Liver of Type 2 Diabetes Mellitus Mice.Metabolites · 2022Article
- Validity of the peak velocity to detect physical training improvements in athymic mice.Frontiers in physiology · 2022Article
- Aerobic Exercise Training Exerts Beneficial Effects Upon Oxidative Metabolism and Non-Enzymatic Antioxidant Defense in the Liver of Leptin Deficiency Mice.Frontiers in endocrinology · 2020Article
- Article
- Retraction Note: Diacerhein attenuates the inflammatory response and improves survival in a model of severe sepsis.Critical care (London, England) · 2016Article
- Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats.Scientific reports · 2016Article
- Vibration exercise decreases insulin resistance and modulates the insulin signaling pathway in a type 2 diabetic rat model.International journal of clinical and experimental medicine · 2015Article
- Physical training improves body weight and energy balance but does not protect against hepatic steatosis in obese mice.International journal of clinical and experimental medicine · 2015Article
- Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its effect on the hepatic glucose production in an insulin resistance state.Diabetology & metabolic syndrome · 2015Article
- Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2014Article
- Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice.The Journal of physiology · 2014Article
- Article
- Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats.FEBS open bio · 2013Article
Corrections and comments
- Expression of concern · 2016-05-06Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Investigation by Journal/Publisher ·
- Expression of concern · 2018-10-15Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Investigation by Company/Institution · Investigation by Journal/Publisher · Upgrade/Update of Prior Notice(s) ·
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein hepatocyte nuclear factor 4alpha (HNF-4alpha) is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. HNF-4alpha and Foxo1 can physically interact with each other and represent an important signal transduction pathway that regulates the synthesis of glucose in the liver. Foxo1 and HNF-4alpha interact with their own binding sites in the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) promoters, and this binding is required for their effects on those promoters. However, the effect of physical activity on the HNF-4alpha/Foxo1 pathway is currently unknown. Here, we investigate the protein levels of HNF-4alpha and the HNF-4alpha/Foxo1 pathway in the liver of leptin-deficient (ob/ob) and diet-induced obese Swiss (DIO) mice after acute exercise. The ob/ob and DIO mice swam for four 30 min periods, with 5 min rest intervals for a total swimming time of 2h. Eight hours after the acute exercise protocol, the mice were submitted to an insulin tolerance test (ITT) and determination of biochemical and molecular parameters. Acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing HNF-4alpha protein levels in the liver of DIO and ob/ob mice under fasting conditions. These phenomena were accompanied by a reduction in the expression of gluconeogenesis genes, such as PEPCK and G6Pase. Importantly, the PI3K inhibitor LY292004 reversed the acute effect of exercise on fasting hyperglycaemia, confirming the involvement of the PI3K pathway. The present study shows that exercise acutely improves the action of insulin in the liver of animal models of obesity and diabetes, resulting in increased phosphorylation and nuclear exclusion of Foxo1, and a reduction in the Foxo1/HNF-4alpha pathway. Since nuclear localization and the association of these proteins is involved in the activation of PEPCK and G6Pase, we believe that the regulation of Foxo1 and HNF-4alpha activities are important mechanisms involved in exercise-induced improvement of glucose homeostasis in insulin resistant states.
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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.