MicroRNAs-mediated epigenetic regulation of GLUT4 protein (Slc2a4 gene) in skeletal muscle of mice with type 2 diabetes mellitus

• Grant number: 17/19449-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2017
• End date: May 10, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ubiratan Fabres Machado
• Grantee: João Victor Del Conti Esteves
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health, AP.TEM

Abstract

Type 2 diabetes mellitus (T2DM) etiopathogeny and pathophysiology are highly related to insulin resistance, a process in which reduced expression of the glucose transporter GLUT4 plays a key role. Recently, epigenetic regulation of several proteins has been related to diabetes; however, nothing is known regarding microRNAs participation on the GLUT4 content reduction in skeletal muscle of T2DM subjects. The present project aims to investigate the epigenetic regulation, mediated by microRNAs, of the GLUT4 protein expression (codified by the Slc2a4 gene) in skeletal muscle of T2DM mice. Firstly, in silico analysis of miRNAs predicted to regulate GLUT4 expression will be performed, and potential candidates will be ranked for further analysis. Further, in T2DM obese mice, the selected miRNAs and Slc2a4 mRNA (RT-qPCR), as well as the GLUT4 protein (Westernblotting) will be quantified in skeletal muscle. Finally, the altered miRNAs will be validated as regulators of GLUT4 expression (overexpression and luciferase assay in HEK-293 cells).

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANDREATO, L. V.; ESTEVES, J. V.; COIMBRA, D. R.; MORAES, A. J. P.; DE CARVALHO, T.. The influence of high-intensity interval training on anthropometric variables of adults with overweight or obesity: a systematic review and network meta-analysis. Obesity Reviews, v. 20, n. 1, p. 142-155, JAN 2019. (17/19449-9)

DAVID-SILVA, ALINE; ESTEVES, JOAO VICTOR; MORAIS, MYCHEL RAONY P. T.; FREITAS, HELAYNE SOARES; ZORN, TELMA MARIA; CORREA-GIANNELLA, MARIA LUCIA; MACHADO, UBIRATAN FABRES. Dual SGLT1/SGLT2 Inhibitor Phlorizin Ameliorates Non-Alcoholic Fatty Liver Disease and Hepatic Glucose Production in Type 2 Diabetic Mice. DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY, v. 13, p. 739-751, 2020. (16/15603-0, 11/09463-8, 17/19449-9)

ESTEVES, V, JOAO; YONAMINE, CAIO Y.; PINTO-JUNIOR, DANILO C.; GERLINGER-ROMERO, FREDERICO; ENGUITA, FRANCISCO J.; MACHADO, UBIRATAN F.. Diabetes Modulates MicroRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p Expression in Muscle: Possible Role in GLUT4 and HK2 Repression. FRONTIERS IN ENDOCRINOLOGY, v. 9, SEP 12 2018. (16/15603-0, 12/20432-0, 12/15514-7, 17/19449-9)

ESTEVES, J.; YONAMINE, C. Y.; GERLINGER-ROMERO, F.; PINTO-JUNIOR, D. C.; ENGUITA, F. J.; MACHADO, U. F.. Diabetes modulates microRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p expression in muscle: potential participation in GLUT4 repression. Diabetologia, v. 61, p. 2-pg., 2018-10-01. (16/15603-0, 17/19449-9)

JULIO, URSULA F.; PANISSA, VALERIA L. G.; CURY, RUBIANA L.; AGOSTINHO, MARCUS F.; ESTEVES, JOAO V. D. C.; FRANCHINI, EMERSON. Energy System Contributions in Upper and Lower Body Wingate Tests in Highly Trained Athletes. RESEARCH QUARTERLY FOR EXERCISE AND SPORT, v. 90, n. 2, MAR 2019. (12/20432-0, 15/11302-3, 17/07304-6, 11/22105-3, 17/08167-2, 17/19449-9)

ESTEVES, J. V.; AMENDOLA, L. S.; OKAMOTO, M. M.; MACHADO, U. F.. Could miR-295-3p be a novel epigenetic regulator of GLUT4?. Diabetologia, v. 65, n. SUPPL 1, p. 1-pg., 2022-09-01. (17/19449-9, 16/15603-0)