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W2896710742 abstract "SUMMARY Gut microbiota changes are associated with increased risk of Type 2 diabetes (T2D) and obesity. Through serum metabolome profiling in patients with cardiometabolic disease (CMD) we identified significant inverse correlation between the microbial metabolite 4-cresol and T2D. Chronic administration of non toxic dose of 4-cresol in two complementary preclinical models of CMD reduced adiposity, glucose intolerance and liver triglycerides, and enhanced insulin secretion in vivo , which may be explained by markedly increased pancreas weight, augmented islet density and size, and enhanced vascularisation suggesting activated islet neogenesis. Incubation of isolated islets with 4-cresol enhanced insulin secretion, insulin content and cell proliferation. In both CMD models 4-cresol treatment in vivo was associated with altered expression of SIRT1 and the kinase DYRK1A, which may contribute to mediate its biological effects. Our findings identify 4-cresol as an effective regulator of β-cell function and T2D endophenotypes, which opens therapeutic perspectives in syndromes of insulin deficiency." @default.
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W2896710742 date "2018-10-16" @default.
W2896710742 modified "2023-10-17" @default.
W2896710742 title "The Microbial Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function" @default.
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W2896710742 doi "https://doi.org/10.1101/444893" @default.
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