Trial reportScientific reports2015
Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRα/POMC pathway.
Trial report in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Metformin monotherapy for adults with type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2020 · on this mapPooled it
- Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2019 · on this mapPooled it
- The effect of metformin and myoinositol on metabolic outcomes in women with polycystic ovary syndrome: role of body mass and adiponectin in a randomized controlled trial.Journal of endocrinological investigation · 2022Trial
- Metformin Increases Cortisol Regeneration by 11βHSD1 in Obese Men With and Without Type 2 Diabetes Mellitus.The Journal of clinical endocrinology and metabolism · 2016Trial
- The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders.Metabolism open · 2025Review
- Molecular Biomarkers and Therapeutic Approach of Patients with Diabetes and Obstructive Sleep Apnea.International journal of molecular sciences · 2025Review
- Analysis of the Endocrine Responses to Anti-Diabetes Drugs: An Issue of Elevated Plasma Renin Concentration in Sodium-Glucose Co-Transporter 2 Inhibitor.International journal of general medicine · 2025Article
- Combination of Metformin and Epigallocatechin-3-Gallate Lowers Cortisol, 11β-Hydroxysteroid Dehydrogenase Type 1, and Blood Glucose Levels in Sprague Dawley Rats with Obesity and Diabetes.Journal of obesity & metabolic syndrome · 2024Article
- Human Aging and Age-Related Diseases: From Underlying Mechanisms to Pro-Longevity Interventions.Aging and disease · 2024Review
- AMPK pathway: an emerging target to control diabetes mellitus and its related complications.Journal of diabetes and metabolic disorders · 2024Review
- Mitigating diabetes associated with reactive oxygen species (ROS) and protein aggregation through pharmacological interventions.RSC advances · 2024Review
- The potential effect of metformin on fibroblast growth factor 21 in type 2 diabetes mellitus (T2DM).Inflammopharmacology · 2023Review
- Association Between Metformin Use and Cognitive and Physical Function in Persons with HIV and Diabetes.AIDS research and human retroviruses · 2023Observational
- Review
- Metformin extends the chronological lifespan of fission yeast by altering energy metabolism and stress resistance capacity.FEMS yeast research · 2023Article
- New Insights into the Role of Insulin and Hypothalamic-Pituitary-Adrenal (HPA) Axis in the Metabolic Syndrome.International journal of molecular sciences · 2022Review
- Physiological Systems in Promoting Frailty.Comprehensive Physiology · 2022Review
- Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions.International journal of molecular sciences · 2022Review
- Pharmacological Approaches to Decelerate Aging: A Promising Path.Oxidative medicine and cellular longevity · 2022Review
- Metabolomic Approaches to Investigate the Effect of Metformin: An Overview.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is a first-line drug for treating type 2 diabetes. Although metformin is known to phosphorylate AMP-activated protein kinase (AMPK), it is unclear how the glucose-lowering effect of metformin is related to AMPK activation. The aim of this study was to identify the urinary endogenous metabolites affected by metformin and to identify the novel underlying molecular mechanisms related to its anti-diabetic effect. Fourteen healthy male subjects were orally administered metformin (1000 mg) once. First morning urine samples were taken before and after administration to obtain metabolomic data. We then further investigated the anti-diabetic mechanism of metformin in vitro and in vivo. The fluctuation of the metabolite cortisol indicated that the neuroendocrine system was involved in the anti-diabetic effect of metformin. Actually we found that metformin induced AMPK/liver X receptor α (LXRα) phosphorylation, followed by pro-opiomelanocortin (POMC) suppression in rat pituitary cells. We confirmed this result by administering metformin in an animal study. Given that cortisol stimulates gluconeogenesis, we propose the anti-hyperglycemic effect of metformin is attributed to reduced POMC/adrenocorticotropic hormone (ACTH)/cortisol levels following AMPK/LXRα phosphorylation in the pituitaries.
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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.