ArticleCell metabolism2020
Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation.
Article in Cell metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed.
- A legume-enriched diet improves metabolic health in prediabetes mediated through gut microbiome: a randomized controlled trial.Nature communications · 2025Trial
- Supplementation of 1-Kestose Modulates the Gut Microbiota Composition to Ameliorate Glucose Metabolism in Obesity-Prone Hosts.Nutrients · 2021Trial
- Magnesium and imidazole propionate.Clinical nutrition ESPEN · 2021Trial
- Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.Nature communications · 2020Trial
- Cardiovascular-kidney-metabolic syndrome through the lens of gut‑derived uremic toxins.Gut microbes · 2026Review
- An oral-gut microbial metabolite linksGut microbes · 2026Article
- Metabolites and cancer metastasis.Oncogene · 2026Review
- From metabolites to membrane vesicles: Unifying gut microbial signals in obesity, t2dm, and MASLD.World journal of microbiology & biotechnology · 2026Review
- Gut microbiota-derived imidazole propionate promotes primary sclerosing cholangitis via p38 signalling.Nature metabolism · 2026Article
- Gut microbiota-derived imidazole propionate predicts cardiometabolic risk in patients with coronary artery disease.European heart journal · 2026Article
- The microbiome regulates host metabolic health and diseases through microbial enzymes.Nature reviews. Gastroenterology & hepatology · 2026Review
- Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology.Nature communications · 2026Article
- Microbiome histidine competition mediates dietary control of systemic imidazole propionate.bioRxiv : the preprint server for biology · 2026Article
- Circulating imidazole propionate and coronary heart disease risk: interplay between histidine intake, fiber, and gut microbiome.BMC medicine · 2026Article
- Enhanced Biodegradation of Cyantraniliprole in Aqueous Systems by Novel Bacterial Consortia: Optimization, Degradation Efficiency, and Bioremediation Potential.Microorganisms · 2026Article
- Microbiota-Derived Metabolites in Developmental Programming: Bridging Early-Life Gut Microbiota to Childhood Metabolic Disorders.Current medical science · 2026Review
- Baicalin Restores the Hypoglycemic Effect of Metformin by Regulating the Microbial Imidazole Propionate and Short-Chain Fatty Acids.Phytotherapy research : PTR · 2026Article
- Investigating the Role of Diet-Manipulated Gut Bacteria in Pathogenesis of Type 2 Diabetes Mellitus-AnNutrients · 2026Article
- Toward a gut-AMPK axis: the microbiome and AMPK signaling in nutrition and healthy aging.Frontiers in physiology · 2026Review
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is the first-line therapy for type 2 diabetes, but there are large inter-individual variations in responses to this drug. Its mechanism of action is not fully understood, but activation of AMP-activated protein kinase (AMPK) and changes in the gut microbiota appear to be important. The inhibitory role of microbial metabolites on metformin action has not previously been investigated. Here, we show that concentrations of the microbial metabolite imidazole propionate are higher in subjects with type 2 diabetes taking metformin who have high blood glucose. We also show that metformin-induced glucose lowering is not observed in mice pretreated with imidazole propionate. Furthermore, we demonstrate that imidazole propionate inhibits AMPK activity by inducing inhibitory AMPK phosphorylation, which is dependent on imidazole propionate-induced basal Akt activation. Finally, we identify imidazole propionate-activated p38γ as a novel kinase for Akt and demonstrate that p38γ kinase activity mediates the inhibitory action of imidazole propionate on metformin.
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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.