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The Natural Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function

Abstract : Exposure to natural metabolites contributes to the risk of cardiometabolic diseases (CMDs). Through metabolome profiling, we identify the inverse correlation between serum concentrations of 4-cresol and type 2 diabetes. The chronic administration of non-toxic doses of 4-cresol in complementary preclinical models of CMD reduces adiposity, glucose intolerance, and liver triglycerides, enhances insulin secretion in vivo, stimulates islet density and size, and pancreatic β-cell proliferation, and increases vascularization, suggesting activated islet enlargement. In vivo insulin sensitivity is not affected by 4-cresol. The incubation of mouse isolated islets with 4-cresol results in enhanced insulin secretion, insulin content, and β-cell proliferation of a magnitude similar to that induced by GLP-1. In both CMD models and isolated islets, 4-cresol is associated with the downregulated expression of the kinase DYRK1A, which may mediate its biological effects. Our findings identify 4-cresol as an effective regulator of β-cell function, which opens up perspectives for therapeutic applications in syndromes of insulin deficiency.
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Contributor : Marc-Emmanuel Dumas Connect in order to contact the contributor
Submitted on : Monday, December 28, 2020 - 12:20:46 PM
Last modification on : Thursday, April 7, 2022 - 1:58:32 PM
Long-term archiving on: : Monday, March 29, 2021 - 6:42:16 PM


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Francois Brial, Fawaz Alzaid, Kazuhiro Sonomura, Yoichiro Kamatani, Kelly Meneyrol, et al.. The Natural Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function. Cell Reports, Elsevier Inc, 2020, 30 (7), pp.2306-2320.e5. ⟨10.1016/j.celrep.2020.01.066⟩. ⟨hal-03089353⟩



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