ArticleMolecular metabolism2022
Insulin resistance per se drives early and reversible dysbiosis-mediated gut barrier impairment and bactericidal dysfunction.
Article in Molecular metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2024Pooled it
- The promising effects of a multi-species synbiotic preparation on metabolic profile in elderly patients with type 2 diabetes and high cardiovascular risk: a randomized, triple-blind, placebo-controlled trial.Nutrition & diabetes · 2025Trial
- Vitamin DBiomolecules · 2026Article
- Interplay between obesity-associated insulin resistance and immune system through the lens of evolutionary medicine.Molecular metabolism · 2026Review
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- Highlights on the Contribution of Gut Microbiota to Immune-Mediated Diseases in Childhood.Mediterranean journal of hematology and infectious diseases · 2026Review
- The Intricate Interplay of Noncoding RNAs and the Gut Microbiome in Gastrointestinal and Endocrine-Related Cancers.Sub-cellular biochemistry · 2026Review
- Elevated Markers of Intestinal Barrier Dysfunction and TLR2 Ligands in Individuals with Type 1 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Gut-liver axis in diabetes: Mechanisms and therapeutic opportunities.World journal of gastroenterology · 2025Review
- Mechanistic Links Between Gut Dysbiosis, Insulin Resistance, and Autism Spectrum Disorder.International journal of molecular sciences · 2025Review
- Anti-Diabetic Effect of Soy-Whey Dual-Protein on Mice with Type 2 Diabetes Mellitus Through INS/IRS1/PI3K Signaling Pathway.Foods (Basel, Switzerland) · 2025Article
- Review
- Nomogram-based risk prediction model employing serum biomarkers to assess intestinal injury risk in patients with metabolic syndrome.Frontiers in endocrinology · 2025Article
- Evaluating the Effects of Sugar ShiftMicroorganisms · 2024Article
- Silicon-Enriched Meat Ameliorates Diabetic Dyslipidemia by Improving Cholesterol, Bile Acid Metabolism and Ileal Barrier Integrity in Rats with Late-Stage Type 2 Diabetes.International journal of molecular sciences · 2024Article
- Article
- Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- The intestinal immune system and gut barrier function in obesity and ageing.The FEBS journal · 2023Review
- Prebiotics Progress Shifts in the Intestinal Microbiome That Benefits Patients with Type 2 Diabetes Mellitus.Biomolecules · 2023Review
- Bacterial DNAemia in Older Participants and Nonagenarian Offspring and Association With Redox Biomarkers: Results From MARK-AGE Study.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveA common feature of metabolic diseases is their association with chronic low-grade inflammation. While enhanced gut permeability and systemic bacterial endotoxin translocation have been suggested as key players of this metaflammation, the mechanistic bases underlying these features upon the diabesity cascade remain partly understood.
methodsHere, we show in mice that, independently of obesity, the induction of acute and global insulin resistance and associated hyperglycemia, upon treatment with an insulin receptor (IR) antagonist (S961), elicits gut hyperpermeability without triggering systemic inflammatory response.
resultsOf note, S961-treated diabetic mice display major defects of gut barrier epithelial functions, such as increased epithelial paracellular permeability and impaired cell-cell junction integrity. We also observed in these mice the early onset of a severe gut dysbiosis, as characterized by the bloom of pro-inflammatory Proteobacteria, and the later collapse of Paneth cells antimicrobial defense. Interestingly, S961 treatment discontinuation is sufficient to promptly restore both the gut microbial balance and the intestinal barrier integrity. Moreover, fecal transplant approaches further confirm that S961-mediated dybiosis contributes at least partly to the disruption of the gut selective epithelial permeability upon diabetic states.
conclusionsTogether, our results highlight that insulin signaling is an indispensable gatekeeper of intestinal barrier integrity, acting as a safeguard against microbial imbalance and acute infections by enteropathogens.
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