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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Esteves, V, Joao ; Yonamine, Caio Y. [1] ; Pinto-Junior, Danilo C. [1] ; Gerlinger-Romero, Frederico [1] ; Enguita, Francisco J. [2] ; Machado, Ubiratan F. [1]
Total Authors: 6
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: FRONTIERS IN ENDOCRINOLOGY; v. 9, SEP 12 2018.
Web of Science Citations: 6
Abstract

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)

FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
Grantee:Ubiratan Fabres Machado
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 12/20432-0 - INVESTIGATION OF miRNAS POTENTIALLY INVOLED IN THE SLC2A4-GLUT4 EXPRESSION REGULATION IN SKELETAL MUSCLE OF DIABETIC RATS
Grantee:João Victor Del Conti Esteves
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 12/15514-7 - Effect of advanced glycated albumin upon Slc2a4 gene in skeletal muscle
Grantee:Danilo Antônio Corrêa Pinto Júnior
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 17/19449-9 - MicroRNAs-mediated epigenetic regulation of GLUT4 protein (Slc2a4 gene) in skeletal muscle of mice with type 2 diabetes mellitus
Grantee:João Victor Del Conti Esteves
Support Opportunities: Scholarships in Brazil - Post-Doctoral