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

Autor:	Brial F; Université de Paris, INSERM UMR 1124, 75006 Paris, France., Alzaid F; Sorbonne Université, Université Paris Descartes, INSERM UMR_S 1138, Cordeliers Research Centre, 75006 Paris, France., Sonomura K; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; Life Science Research Center, Technology Research Laboratory, Shimadzu, Kyoto 604-8511, Japan., Kamatani Y; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan., Meneyrol K; Université de Paris, Unit of Functional and Adaptive Biology, UMR 8251, CNRS, 4 rue Marie Andrée Lagroua Weill-Halle, 75013 Paris, France., Le Lay A; Université de Paris, INSERM UMR 1124, 75006 Paris, France., Péan N; Université de Paris, INSERM UMR 1124, 75006 Paris, France., Hedjazi L; Université de Paris, INSERM UMR 1124, 75006 Paris, France., Sato TA; Life Science Research Center, Technology Research Laboratory, Shimadzu, Kyoto 604-8511, Japan., Venteclef N; Sorbonne Université, Université Paris Descartes, INSERM UMR_S 1138, Cordeliers Research Centre, 75006 Paris, France., Magnan C; Université de Paris, Unit of Functional and Adaptive Biology, UMR 8251, CNRS, 4 rue Marie Andrée Lagroua Weill-Halle, 75013 Paris, France., Lathrop M; McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, QC H3A 0G1, Canada., Dumas ME; 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 SW7 2AZ, UK., Matsuda F; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan., Zalloua P; Lebanese American University, School of Medicine, Beirut 1102 2801, Lebanon. Electronic address: pierre.zalloua@lau.edu.lb., Gauguier D; Université de Paris, INSERM UMR 1124, 75006 Paris, France; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan; McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, QC H3A 0G1, Canada. Electronic address: dominique.gauguier@crc.jussieu.fr.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Feb 18; Vol. 30 (7), pp. 2306-2320.e5.
DOI:	10.1016/j.celrep.2020.01.066
Abstrakt:	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. Competing Interests: Declaration of Interests F.B., F.M., P.Z., and D.G. are named inventors on a patent related to this work (Ref. EP 17306326). K.S. and T.-A.S. are employees of Shimadzu (Kyoto, Japan). F.A., Y.K., K.M., A.L.L., N.P., L.H., N.V., C.M., M.L., and M.-E.D. declare no competing financial interests. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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