The following study was conducted by Scientists from Université de Paris, INSERM, Paris, France; Université de Paris, Unit of Functional and Adaptive Biology, Paris, France; Sorbonne Université, Université Paris Descartes, INSERM, Cordeliers Research Centre, Paris, France; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; Life Science Research Center, Technology Research Laboratory, Shimadzu, Kyoto, Japan; Université de Paris, Unit of Functional and Adaptive Biology, Paris, France; McGill University and Genome Quebec Innovation Centre, Montreal, Canada; Imperial College London, Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Sir Alexander Fleming Building, London, UK; Lebanese American University, School of Medicine, Beirut, Lebanon. Study is published in Nature Communications Journal as detailed below.
Cell Reports; 30(7): 2306-2320.e2305; (2020)
The Natural Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function
Highlights
- Serum concentrations of 4-cresol are inversely correlated with type 2 diabetes
- Non-toxic dose of 4-cresol reduces adiposity, glucose intolerance, and liver fat
- 4-Cresol stimulates insulin secretion and β-cell proliferation in vivo and in vitro
- 4-Cresol downregulates pancreatic and islet expression of the kinase DYRK1A
Summary
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.
Source:
Cell Reports
URL: https://www.sciencedirect.com/science/article/pii/S2211124720300917
Citation:
Brial, F., F. Alzaid, et al. (2020). “The Natural Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function.” Cell Reports 30(7): 2306-2320.e2305.
