ArticleNature communications2019
Inhibition of upper small intestinal mTOR lowers plasma glucose levels by inhibiting glucose production.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Metformin as a Multifaceted Therapeutic Agent for Gastrointestinal Diseases: Mechanisms, Clinical Efficacy, and Future Directions.Pharmacology research & perspectives · 2026Review
- Neuroimmune interactions: The bridge between inflammatory bowel disease and the gut microbiota.Clinical and translational medicine · 2025Review
- Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.Current medicinal chemistry · 2025Review
- Arf1 promotes porcine intestinal epithelial cell proliferation via the mTORC1 signaling pathway.In vitro cellular & developmental biology. Animal · 2024Article
- Molecular mechanisms of action of metformin: latest advances and therapeutic implications.Clinical and experimental medicine · 2023Review
- Metabolic regulation by the intestinal metformin-AMPK axis.Nature communications · 2022Article
- Targeting colonic macrophages improves glycemic control in high-fat diet-induced obesity.Communications biology · 2022Article
- An update on mode of action of metformin in modulation of meta-inflammation and inflammaging.Pharmacological reports : PR · 2022Review
- Metabolic reprogramming by driver mutation-tumor microenvironment interplay in pancreatic cancer: new therapeutic targets.Cancer metastasis reviews · 2021Review
- P53 mediates the protective effects of metformin in inflamed lung endothelial cells.International immunopharmacology · 2021Article
- Microecological preparation combined with an modified low-carbon diet improves glucolipid metabolism and cardiovascular complication in obese patients.Diabetology & metabolic syndrome · 2021Article
- Ageing, metabolism and the intestine.EMBO reports · 2020Review
- Metabolic and immunologic control of intestinal cell function by mTOR.International immunology · 2020Review
- Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucose homeostasis is partly controlled by the energy sensor mechanistic target of rapamycin (mTOR) in the muscle and liver. However, whether mTOR in the small intestine affects glucose homeostasis in vivo remains unknown. Here, we first report that delivery of rapamycin or an adenovirus encoding the dominant negative acting mTOR-mutated protein into the upper small intestine is sufficient to inhibit small intestinal mTOR signaling and lower glucose production in rodents with high fat diet-induced insulin resistance. Second, we found that molecular activation of small intestinal mTOR blunts the glucose-lowering effect of the oral anti-diabetic agent metformin, while inhibiting small intestinal mTOR alone lowers plasma glucose levels by inhibiting glucose production in rodents with diabetes as well. Thus, these findings illustrate that inhibiting upper small intestinal mTOR is sufficient and necessary to lower glucose production and enhance glucose homeostasis, and thereby unveil a previously unappreciated glucose-lowering effect of small intestinal mTOR.
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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.