Resveratrol Improves Glycemic Control in Type 2 Diabetic Obese Mice by Regulating Glucose Transporter Expression in Skeletal Muscle and Liver.

Autor: Yonamine CY; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil. caioyogi@icb.usp.br., Pinheiro-Machado E; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil. erika.pinheiro.machado@usp.br., Michalani ML; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil. maria.michalani@usp.br., Alves-Wagner AB; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil. anabarbara_ta@yahoo.com.br., Esteves JV; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil. joaovesteves@gmail.com., Freitas HS; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil. hfreitas@icb.usp.br., Machado UF; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Av. Prof. Lineu Prestes 1524, São Paulo 05508-900, Brazil. ubiratan@icb.usp.br.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2017 Jul 14; Vol. 22 (7). Date of Electronic Publication: 2017 Jul 14.
DOI: 10.3390/molecules22071180
Abstrakt: Insulin resistance participates in the glycaemic control disruption in type 2 diabetes mellitus (T2DM), by reducing muscle glucose influx and increasing liver glucose efflux. GLUT4 ( Slc2a4 gene) and GLUT2 ( Slc2a2 gene) proteins play a fundamental role in the muscle and liver glucose fluxes, respectively. Resveratrol is a polyphenol suggested to have an insulin sensitizer effect; however, this effect, and related mechanisms, have not been clearly demonstrated in T2DM. We hypothesized that resveratrol can improve glycaemic control by restoring GLUT4 and GLUT2 expression in muscle and liver. Mice were rendered obese T2DM in adult life by neonatal injection of monosodium glutamate. Then, T2DM mice were treated with resveratrol for 60 days or not. Glycaemic homeostasis, GLUT4, GLUT2, and SIRT1 (sirtuin 1) proteins (Western blotting); Slc2a4 , Slc2a2 , and Pck1 (key gluconeogenic enzyme codifier) mRNAs (RT-qPCR); and hepatic glucose efflux were analysed. T2DM mice revealed: high plasma concentration of glucose, fructosamine, and insulin; insulin resistance (insulin tolerance test); decreased Slc2a4 /GLUT4 content in gastrocnemius and increased Slc2a2 /GLUT2 content in liver; and increased Pck1 mRNA and gluconeogenic activity (pyruvate tolerance test) in liver. All alterations were restored by resveratrol treatment. Additionally, in both muscle and liver, resveratrol increased SIRT1 nuclear content, which must participate in gene expression regulations. In sum, the results indisputably reveals that resveratrol improves glycaemic control in T2DM, and that involves an increase in muscle Slc2a4 /GLUT4 and a decrease in liver Slc2a2 /GLUT2 expression. This study contributes to our understanding how resveratrol might be prescribed for T2DM according to the principles of evidence-based medicine.
Competing Interests: The authors have nothing to disclose.
Databáze: MEDLINE
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