The Natural Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function - Archive ouverte HAL Access content directly
Journal Articles Cell Reports Year : 2020

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

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Fawaz Alzaid
Taka-Aki Sato
  • Function : Author
Marc-Emmanuel Dumas

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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Dates and versions

hal-03089353 , version 1 (28-12-2020)

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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, 2020, 30 (7), pp.2306-2320.e5. ⟨10.1016/j.celrep.2020.01.066⟩. ⟨hal-03089353⟩
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