ArticleScientific reports2021
Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 101 citations in OpenAlex.
- Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans.Frontiers in endocrinology · 2026Trial
- Post-COVID impairment of T cell responses to community-acquired pathogens can be modified by activating cellular metabolism.PLoS pathogens · 2026Article
- PPARβ/δ contributes to the antidiabetic effect and the increase in GDF15 caused by metformin.Acta pharmacologica Sinica · 2026Article
- Metformin treatment impairs the adenine nucleotide translocator activity and energy metabolism in human clear cell renal carcinoma cells.Scientific reports · 2026Article
- Illuminating Glucose: How to Unveil Organ-Specific Insulin Resistance and Guide Metabolic Strategies in Diabetes.Diabetes/metabolism research and reviews · 2026Review
- Post-COVID impairment of memory T cell responses to community-acquired pathogens can be rectified by activating cellular metabolism.bioRxiv : the preprint server for biology · 2026Article
- Metformin Alone and in Combinations Alter the Methylation Patterns ofEndocrine, metabolic & immune disorders drug targets · 2026Article
- Porous-starch-encapsulated quercetin remodels the gut microbiota and elevates short-chain fatty acids, alleviating hyperglycaemia-associated phenotypes in T2DM mice.Frontiers in nutrition · 2026Article
- Novel mechanism whereby metformin improves glucose homeostasis: TXNIP-GLUT1 axis modulation enhances intestinal glucotonic effects.Experimental & molecular medicine · 2025Article
- Disruption of glutamine transport uncouples the NUPR1 stress-adaptation program and induces prostate cancer radiosensitivity.Cell communication and signaling : CCS · 2025Article
- N-Lactoyl Amino Acids: Emerging Biomarkers in Metabolism and Disease.Diabetes/metabolism research and reviews · 2025Review
- Targeting the Electron Transport System for Enhanced Longevity.Biomolecules · 2025Review
- Antifungal effects of Metformin against Candida albicans by autophagy regulation.Journal of microbiology (Seoul, Korea) · 2025Article
- STX1A regulates ferroptosis and chemoresistance in gastric cancer through mitochondrial function modulation.Human cell · 2025Article
- Metformin-regulated glucose flux from the circulation to the intestinal lumen.Communications medicine · 2025Article
- Individual bioenergetic capacity as a potential source of resilience to Alzheimer's disease.Nature communications · 2025Article
- Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.International journal of molecular sciences · 2025Review
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- Organoids for Obesity-related Diseases: Disease Models and Drug Screening.Current stem cell research & therapy · 2025Review
- Metformin modulates oxidative stress via activation of AMPK/NF-κB signaling in Trisomy 21 fibroblasts: anFrontiers in molecular biosciences · 2025Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Even though metformin is widely used to treat type2 diabetes, reducing glycaemia and body weight, the mechanisms of action are still elusive. Recent studies have identified the gastrointestinal tract as an important site of action. Here we used intestinal organoids to explore the effects of metformin on intestinal cell physiology. Bulk RNA-sequencing analysis identified changes in hexose metabolism pathways, particularly glycolytic genes. Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates. Metformin caused mitochondrial dysfunction and metformin's effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss. Gene expression changes elicited by metformin were replicated in 3D apical-out organoids and distal small intestines of metformin treated mice. We conclude that metformin affects glucose uptake, glycolysis and GDF-15 secretion, likely downstream of the observed mitochondrial dysfunction. This may explain the effects of metformin on intestinal glucose utilisation and food balance.
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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.