Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu, Republic of Korea.
Mol Nutr Food Res. 2012 Aug;56(8):1282-91. doi: 10.1002/mnfr.201200067. Epub 2012 Jun 20.
This study investigated the effects of resveratrol (RV) on diabetes-related metabolic changes in a spontaneous model of type 2 diabetes, as well as activation of AMP-activated protein kinase (AMPK) and downstream targets.
C57BL/KsJ-db/db mice were fed a normal diet with RV (0.005% and 0.02%, w/w) or rosiglitazone (RG, 0.001%, w/w) for 6 weeks. Both doses of RV significantly decreased blood glucose, plasma free fatty acid, triglyceride, apo B/apo AІ levels and increased plasma adiponectin levels. RV activated AMPK and downstream targets leading to decreased blood HbA1c levels, hepatic gluconeogenic enzyme activity, and hepatic glycogen, while plasma insulin levels, pancreatic insulin protein, and skeletal muscle GLUT4 protein were higher after RV supplementation. The high RV dose also significantly increased hepatic glycolytic gene expression and enzyme activity, along with skeletal muscle glycogen synthase protein expression, similar to RG. Furthermore, RV dose dependently decreased hepatic triglyceride content and phosphorylated I kappa B kinase (p-IKK) protein expression, while hepatic uncoupling protein (UCP) and skeletal muscle UCP expression were increased.
RV potentiates improving glycemic control, glucose uptake, and dyslipidemia, as well as protecting against pancreatic β-cell failure in a spontaneous type 2 diabetes model. Dietary RV has potential as an antidiabetic agent via activation of AMPK and its downstream targets.
本研究旨在探讨白藜芦醇（RV）对 2 型糖尿病自发模型中与糖尿病相关的代谢变化的影响，以及对 AMP 激活的蛋白激酶（AMPK）及其下游靶点的激活作用。
C57BL/KsJ-db/db 小鼠喂食含 RV（0.005%和 0.02%，w/w）或罗格列酮（RG，0.001%，w/w）的正常饮食 6 周。RV 的两个剂量均显著降低血糖、血浆游离脂肪酸、甘油三酯、载脂蛋白 B/载脂蛋白 AІ 水平，并增加血浆脂联素水平。RV 激活 AMPK 及其下游靶点，导致 HbA1c 水平降低，肝糖异生酶活性和肝糖原降低，而 RV 补充后血浆胰岛素水平、胰腺胰岛素蛋白和骨骼肌 GLUT4 蛋白升高。高 RV 剂量还显著增加肝糖酵解基因表达和酶活性，以及骨骼肌糖原合酶蛋白表达，与 RG 相似。此外，RV 剂量依赖性地降低肝甘油三酯含量和磷酸化 I kappa B 激酶（p-IKK）蛋白表达，同时增加肝解偶联蛋白（UCP）和骨骼肌 UCP 表达。
RV 可增强改善血糖控制、葡萄糖摄取和血脂异常，并在 2 型糖尿病自发模型中防止胰岛β细胞衰竭。膳食 RV 通过激活 AMPK 及其下游靶点，具有作为抗糖尿病药物的潜力。
