ArticleBiomolecules2021
Metformin Targets Foxo1 to Control Glucose Homeostasis.
Article in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- MicroRNAs modulated by DPP-4 inhibitor and bedtime NPH insulin therapy in individuals with type 2 diabetes.Frontiers in endocrinology · 2025Trial
- Forkhead Box O1 Promotes Osteogenesis of Periodontal Ligament Stem Cells Via Glycolysis-Related Metabolic Reprogramming.International dental journal · 2026Article
- Construction of a Three-Dimensional Calcific Aortic Valve Disease Model Using Human iPSC-Derived Valvular Interstitial Cells.Stem cell reviews and reports · 2026Article
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- Metformin Mitigates Diabetes-Driven Renal Senescence via Immunomodulation and the FABP4/FOXO1 Axis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- A prognostic signature based on insulin-signaling-pathway genes for hepatocellular carcinoma.Discover oncology · 2025Article
- β-cell dedifferentiation in type 2 diabetes: Interplay of metabolic stress, endoplasmic reticulum dysfunction, and forkhead box protein O1 inhibition.World journal of diabetes · 2025Article
- Metformin's Effects on Cognitive Function from a Biovariance Perspective: A Narrative Review.International journal of molecular sciences · 2025Review
- Metformin in gestational diabetes: physiological actions and clinical applications.Nature reviews. Endocrinology · 2025Review
- Imeglimin enhances glucagon secretion through an indirect mechanism and improves fatty liver in high-fat, high-sucrose diet-fed mice.Journal of diabetes investigation · 2024Article
- Early life interventions metformin and trodusquemine metabolically reprogram the developing mouse liver through transcriptomic alterations.Aging cell · 2024Article
- TGF-β1 Signaling Impairs Metformin Action on Glycemic Control.International journal of molecular sciences · 2024Article
- Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells.Exploration of targeted anti-tumor therapy · 2024Article
- Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus.Nutrients · 2023Review
- Hepatic p38α MAPK controls gluconeogenesis via FOXO1 phosphorylation at S273 during glucagon signalling in mice.Diabetologia · 2023Article
- FoxO1 as a tissue-specific therapeutic target for type 2 diabetes.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus (T2D). Metformin exerts its glucose-lowering effect primarily through decreasing hepatic glucose production (HGP). However, the precise molecular mechanisms of metformin remain unclear due to supra-pharmacological concentration of metformin used in the study. Here, we investigated the role of Foxo1 in metformin action in control of glucose homeostasis and its mechanism via the transcription factor Foxo1 in mice, as well as the clinical relevance with co-treatment of aspirin. We showed that metformin inhibits HGP and blood glucose in a Foxo1-dependent manner. Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA→Foxo1 signaling pathway. In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP. We further showed that metformin attenuates PKA activity, decreases Foxo1-S273 phosphorylation, and improves glucose homeostasis in diet-induced obese mice. We also provided evidence that salicylate suppresses HGP and blood glucose through the PKA→Foxo1 signaling pathway, but it has no further additive improvement with metformin in control of glucose homeostasis. Our study demonstrates that metformin inhibits HGP through PKA-regulated transcription factor Foxo1 and its S273 phosphorylation.
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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.