Diabetes Modulates MicroRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p Expression in Muscle: Possible Role in GLUT4 and HK2 Repression

Autor(es)

Esteves, V, Joao ; Yonamine, Caio Y. ^[1] ; Pinto-Junior, Danilo C. ^[1] ; Gerlinger-Romero, Frederico ^[1] ; Enguita, Francisco J. ^[2] ; Machado, Ubiratan F. ^[1]

Afiliação do(s) autor(es)

^[1] Esteves, Joao, V, Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Univ Lisbon, Fac Med, Inst Med Mol, Lisbon - Portugal

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ENDOCRINOLOGY; v. 9, SEP 12 2018.
• Citações Web of Science: 6

Resumo

The reduced expression of solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) and hexokinase-2 (HK2) in skeletal muscle participates in insulin resistance of diabetes mellitus (DM). MicroRNAs (miRNAs) have emerged as important modulators of mRNA/protein expression, but their role in DM is unclear. We investigated miRNAs hypothetically involved in GLUT4/HK2 expression in soleus muscle of type 1 diabetes-like rats. In silico analysis revealed 651 miRNAs predicted to regulate solute carrier family 2 member 4 (Slc2a4) mRNA, several of them also predicted to regulate Hk2 mRNA, and 16 miRNAs were selected for quantification. Diabetes reduced Slc2a4/GLUT4 and Hk2/HK2 expression (50-77%), upregulated miR-29b-3p and miR-29c-3p (50-100%), and downregulated miR-93-5p, miR-150-5p, miR-199a-5p, miR-345-3p, and miR-532-3p (similar to 30%) expression. Besides, GLUT4 and HK2 proteins correlated (P < 0.05) negatively with miR-29b-3p and miR-29c-3p and positively with miR-199a-5p and miR-532-3p, suggesting that these miRNAs could be markers of alterations in GLUT4 and HK2 expression. Additionally, diabetes increased the nuclear factor kappa B subunit 1 protein (p50) expression, a repressor of Slc2a4, which was also predicted as a target for miR-199a-5p and miR-532-3p. Correlations were also detected between these miRNAs and blood glucose, 24-h glycosuria and plasma fructosamine, and insulin therapy reversed most of the alterations. In sum, we report that diabetes altered miR-29b-3p, miR-29c-3p, miR-199a-5p and miR-532-3p expression in muscle of male rats, where their predicted targets Slc2a4/GLUT4 and Hk2/HK2 are repressed. These data shed light on these miRNAs as a markers of impaired skeletal muscle glucose disposal, and, consequently, glycemic control in diabetes. (AU)

• Processo FAPESP: 16/15603-0 - Desvendando mecanismos envolvidos no controle glicêmico e nas complicações crônicas do Diabetes mellitus: contribuições à saúde humana
• Beneficiário: Ubiratan Fabres Machado
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/20432-0 - AVALIAÇÃO DE miRNAs POTENCIALMENTE REGULADORES DA EXPRESSÃO DE Slc2a4/GLUT4 EM MÚSCULO ESQUELÉTICO DE RATOS DIABÉTICOS
• Beneficiário: João Victor Del Conti Esteves
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/15514-7 - Efeito in vitro da albumina modificada por glicação avançada sobre a expressão do gene Slc2a4 em músculo esquelético
• Beneficiário: Danilo Antônio Corrêa Pinto Júnior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/19449-9 - Regulação epigenética, mediada por microRNAs, da proteína GLUT4 (gene Slc2a4) em músculo esquelético de camundongos portadores de diabetes mellitus tipo 2
• Beneficiário: João Victor Del Conti Esteves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado