Diabetes modulates microRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p expression in muscle: possible role in GLUT4 and HK2 repression

Esteves, João V, Yonamine, Caio Y, Pinto-Junior, Danilo C, Gerlinger Romero, Frederico, Enguita, Francisco J and Machado, Ubiratan F 2018, 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, vol. 9, pp. 1-12, doi: 10.3389/fendo.2018.00536.

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Title Diabetes modulates microRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p expression in muscle: possible role in GLUT4 and HK2 repression
Author(s) Esteves, João V
Yonamine, Caio Y
Pinto-Junior, Danilo C
Gerlinger Romero, FredericoORCID iD for Gerlinger Romero, Frederico orcid.org/0000-0002-2150-0384
Enguita, Francisco J
Machado, Ubiratan F
Journal name Frontiers in endocrinology
Volume number 9
Article ID 536
Start page 1
End page 12
Total pages 12
Publisher Frontiers Media
Place of publication Lausanne, Switzerland
Publication date 2018-09
ISSN 1664-2392
Keyword(s) microRNA
skeletal muscle
GLUT4
hexokinase
glucose metabolism
glucose uptake
NFKB
streptozotocin
Summary 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 (∼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.
Language eng
DOI 10.3389/fendo.2018.00536
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, Esteves, Yonamine, Pinto-Junior, Gerlinger-Romero, Enguita and Machado
Persistent URL http://hdl.handle.net/10536/DRO/DU:30115641

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
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