Diabetes induces tri-methylation at lysine 9 of histone 3 at Slc2a4 gene in skeletal muscle: A new target to improve glycemic control.

Autor: Yonamine CY; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: caioyogi@icb.usp.br., Alves-Wagner AB; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Esteves JV; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Okamoto MM; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Correa-Giannella ML; Laboratório de Carboidratos e Radioimunoensaio, LIM-18, Hospital das Clinicas HCFMUSP, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil; Programa de Pos-Graduaçao em Medicina, Universidade Nove de Julho (UNINOVE), Sao Paulo, Brazil., Giannella-Neto D; Programa de Pos-Graduaçao em Medicina, Universidade Nove de Julho (UNINOVE), Sao Paulo, Brazil., Machado UF; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2019 Feb 05; Vol. 481, pp. 26-34. Date of Electronic Publication: 2018 Dec 06.
DOI: 10.1016/j.mce.2018.11.006
Abstrakt: Expression of the glucose transporter GLUT4, encoded by Slc2a4 gene, is reduced in both type 1 and type 2 diabetes (T1D and T2D), contributing to glycemic impairment. The present study investigated epigenetic regulations at the Slc2a4 promoter in skeletal muscle of T1D- and T2D-like experimental models. Slc2a4/GLUT4 repression was observed in T1D and T2D and that was reversed by insulin and resveratrol treatments, respectively. In both T1D-like and T2D-like animals, tri-methylation at lysine 9 of histone 3 (H3K9me3) increased in the Slc2a4 enhancer segment, whereas MEF2A/D binding into this segment was reduced; all effects were reversed by respective treatments. This study reveals that increased H3K9me3 in the Slc2a4 promoter enhancer segment contributes to reduce GLUT4 expression in skeletal muscle and to worse glycemic control in diabetes, pointing to the H3K9me3 of Slc2a4 promoter as a potential target for development of new approaches for treating diabetes.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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