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

机译:白藜芦醇通过调节骨骼肌和肝脏中葡萄糖转运蛋白的表达来改善2型糖尿病肥胖小鼠的血糖控制。

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摘要

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.
机译:胰岛素抵抗通过减少肌肉葡萄糖流入和增加肝糖外排参与2型糖尿病(T2DM)的血糖控制破坏。 GLUT4(Slc2a4基因)和GLUT2(Slc2a2基因)蛋白分别在肌肉和肝脏的葡萄糖通量中起基本作用。白藜芦醇是一种多酚,被认为具有胰岛素增敏作用。但是,这种效果和相关机制尚未在T2DM中明确证明。我们假设白藜芦醇可以通过恢复肌肉和肝脏中的GLUT4和GLUT2表达来改善血糖控制。通过新生儿注射谷氨酸钠使小鼠在成年后变成肥胖的T2DM。然后,用白藜芦醇治疗T2DM小鼠60天或不治疗。血糖动态平衡,GLUT4,GLUT2和SIRT1(sirtuin 1)蛋白(蛋白质印迹); Slc2a4,Slc2a2和Pck1(关键糖异生酶编码剂)mRNA(RT-qPCR);并进行肝葡萄糖外排。 T2DM小鼠显示:血浆,葡萄糖,果糖胺和胰岛素的血药浓度较高;胰岛素抵抗(胰岛素耐受性测试);腓肠肌中Slc2a4 / GLUT4含量降低,肝脏中Slc2a2 / GLUT2含量升高;并增加肝脏中Pck1 mRNA和糖原异生活性(丙酮酸耐受性试验)。白藜芦醇治疗可恢复所有改变。此外,在肌肉和肝脏中,白藜芦醇都会增加SIRT1的核含量,必须参与基因表达调控。总之,结果无可争议地表明白藜芦醇改善了T2DM中的血糖控制,并且涉及肌肉Slc2a4 / GLUT4的增加和肝脏Slc2a2 / GLUT2表达的减少。这项研究有助于我们了解如何根据循证医学原则为T2DM处方白藜芦醇。

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