ArticleActa pharmacologica Sinica2016
Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling.
Article in Acta pharmacologica Sinica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies.Frontiers in endocrinology · 2020Pooled it
- Pooled it
- The Gut-Insulin Axis in Polycystic Ovary Syndrome: A Narrative Review of Gut Dysbiosis, Inflammation, and Emerging Therapeutic Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Oxidative Stress as a Pathophysiological Core of Obesity: Preclinical Evidence for Antioxidant-Based Therapy Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Revisiting Insulin Resistance in the Pathophysiology of Type 2 Diabetes Mellitus: A Multi-Organ Perspective.Diabetes & metabolism journal · 2026Review
- Metformin enhances survival with immune checkpoint inhibitors in cancer patients: A meta-analysis.Oncology letters · 2026Article
- The Gut Microbiota-Related Antihyperglycemic Effect of Metformin.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Sex differences in the skeletal muscle response to metformin treatment and the possible association with gut-muscle axis in rats.Frontiers in endocrinology · 2025Article
- Gut microbiota: an emerging target connecting polycystic ovarian syndrome and insulin resistance.Frontiers in cellular and infection microbiology · 2025Review
- Bixin Combined with Metformin Ameliorates Insulin Resistance and Antioxidant Defenses in Obese Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Rethinking about Metformin: Promising Potentials.Korean journal of family medicine · 2024Article
- The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetes care · 2024Review
- Review
- The gut microbiota and diabetes: research, translation, and clinical applications - 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2024Review
- Metformin: Past, Present, and Future.Current diabetes reports · 2024Review
- OptimizingMicroorganisms · 2024Article
- Advances in the mechanism of metformin with wide-ranging effects on regulation of the intestinal microbiota.Frontiers in microbiology · 2024Review
- Understanding the action mechanisms of metformin in the gastrointestinal tract.Frontiers in pharmacology · 2024Review
- Metformin: update on mechanisms of action and repurposing potential.Nature reviews. Endocrinology · 2023Review
- Obesity-induced inflammation exacerbates clonal hematopoiesis.The Journal of clinical investigation · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimAccumulating evidence shows that lipopolysaccharides (LPS) derived from gut gram-negative bacteria can be absorbed, leading to endotoxemia that triggers systemic inflammation and insulin resistance. In this study we examined whether metformin attenuated endotoxemia, thus improving insulin signaling in high-fat diet fed mice.
methodsMice were fed a high-fat diet for 18 weeks to induce insulin resistance. One group of the mice was treated with oral metformin (100 mg·kg(-1)·d(-1)) for 4 weeks. Another group was treated with LPS (50 μg·kg(-1)·d(-1), sc) for 5 days followed by the oral metformin for 10 d. Other two groups received a combination of antibiotics for 7 d or a combination of antibiotics for 7 d followed by the oral metformin for 4 weeks, respectively. Glucose metabolism and insulin signaling in liver and muscle were evaluated, the abundance of gut bacteria, gut permeability and serum LPS levels were measured.
resultsIn high-fat fed mice, metformin restored the tight junction protein occludin-1 levels in gut, reversed the elevated gut permeability and serum LPS levels, and increased the abundance of beneficial bacteria Lactobacillus and Akkermansia muciniphila. Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IκBα in liver and muscle of the mice. Treatment with exogenous LPS abolished the beneficial effects of metformin on glucose metabolism, insulin signaling and oxidative stress in liver and muscle of the mice. Treatment with antibiotics alone produced similar effects as metformin did. Furthermore, the beneficial effects of antibiotics were addictive to those of metformin.
conclusionMetformin administration attenuates endotoxemia and enhances insulin signaling in high-fat fed mice, which contributes to its anti-diabetic effects.
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Registered trials
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