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通过改变肝脏和骨骼肌中的信号通路,白藜芦醇改善代谢综合征猪模型的葡萄糖代谢。

Improving glucose metabolism with resveratrol in a swine model of metabolic syndrome through alteration of signaling pathways in the liver and skeletal muscle.

作者信息

Burgess Thomas A, Robich Michael P, Chu Louis M, Bianchi Cesario, Sellke Frank W

机构信息

Division of Cardiothoracic Surgery, Department of Surgery, and Cardiovascular Research Center, Rhode Island Hospital, Providence, USA.

出版信息

Arch Surg. 2011 May;146(5):556-64. doi: 10.1001/archsurg.2011.100.

DOI:10.1001/archsurg.2011.100
PMID:21739664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3285438/
Abstract

HYPOTHESIS

We hypothesized that supplemental resveratrol would affect glucose metabolism in the skeletal muscle and liver to improve blood glucose control.

DESIGN

Case-control study.

SETTING

Hospital laboratory.

SUBJECTS

Yorkshire miniswine.

INTERVENTION

The swine developed metabolic syndrome by consuming a high-calorie, high–fat/cholesterol diet for 11 weeks. Pigs were fed either a normal diet (control) (n = 7), a hypercholesterolemic diet (HCC) (n = 7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d) (HCRV) (n = 7). Animals underwent dextrose challenge prior to euthanasia and tissue collection.

MAIN OUTCOME MEASURES

Measurements of glucose and insulin levels, skeletal muscle and liver protein expression, and liver function test results.

RESULTS

The HCC group had significantly increased blood glucose levels at 30 minutes as compared with the control and HCRV groups. The HCC group demonstrated increased fasting serum insulin levels and levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Oil red O staining demonstrated increased lipid deposition in the livers of the HCC animals. Immunoblotting in the liver showed increased levels of mammalian target of rapamycin, insulin receptor substrate 1, and phosphorylated AKT in the HCRV group. Immunoblotting in skeletal muscle tissue demonstrated increased glucose transporter type 4 (Glut 4), peroxisome proliferating activation receptor coactivator 1α, peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor , and phosphorylated AKT at threonine 308 expression as well as decreased retinol binding protein 4 in the HCRV group. Immunofluorescence staining for Glut 4 in the skeletal muscle demonstrated increased Glut 4 staining in the HCRV group compared with the HCC or control groups.

CONCLUSION

Supplemental resveratrol positively influences glucose metabolism pathways in the liver and skeletal muscle and leads to improved glucose control in a swine model of metabolic syndrome.

摘要

假设

我们假设补充白藜芦醇会影响骨骼肌和肝脏中的葡萄糖代谢,从而改善血糖控制。

设计

病例对照研究。

地点

医院实验室。

研究对象

约克夏小型猪。

干预措施

猪通过食用高热量、高脂肪/胆固醇饮食11周而患上代谢综合征。将猪分为三组,分别给予正常饮食(对照组)(n = 7)、高胆固醇饮食(HCC)(n = 7)或添加白藜芦醇(100 mg/kg/天)的高胆固醇饮食(HCRV)(n = 7)。在安乐死和组织采集前对动物进行葡萄糖耐量试验。

主要观察指标

测量血糖和胰岛素水平、骨骼肌和肝脏蛋白表达以及肝功能测试结果。

结果

与对照组和HCRV组相比,HCC组在30分钟时血糖水平显著升高。HCC组空腹血清胰岛素水平以及天冬氨酸转氨酶、丙氨酸转氨酶和碱性磷酸酶水平升高。油红O染色显示HCC组动物肝脏脂质沉积增加。肝脏免疫印迹显示HCRV组雷帕霉素靶蛋白、胰岛素受体底物1和磷酸化AKT水平升高。骨骼肌组织免疫印迹显示HCRV组4型葡萄糖转运蛋白(Glut 4)、过氧化物酶体增殖物激活受体γ辅激活因子1α、过氧化物酶体增殖物激活受体α、过氧化物酶体增殖物激活受体γ以及苏氨酸308位点磷酸化AKT表达增加,视黄醇结合蛋白4表达减少。骨骼肌中Glut 4的免疫荧光染色显示,与HCC组或对照组相比,HCRV组Glut 4染色增加。

结论

在代谢综合征猪模型中,补充白藜芦醇对肝脏和骨骼肌中的葡萄糖代谢途径有积极影响,并能改善血糖控制。

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