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脂联素在高脂饮食喂养的小鼠胰腺中表达,并在 2 型糖尿病发展过程中保护胰腺内皮功能。

Adiponectin is expressed in the pancreas of high-fat-diet-fed mice and protects pancreatic endothelial function during the development of type 2 diabetes.

机构信息

Department of Cell Biology, Peking University Health Science Center, Beijing 100191, China.

Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.

出版信息

Diabetes Metab. 2014 Nov;40(5):363-72. doi: 10.1016/j.diabet.2014.05.004. Epub 2014 Jun 27.

Abstract

AIM

Adiponectin levels in skeletal muscle and adipose tissue have been reported to be involved in insulin resistance in rats fed with a high-fat diet (HFD). Our objective was to explore whether adiponectin is also expressed in the pancreas and what its potential role is during the development of type 2 diabetes (T2D) in outbred CD-1 mice.

METHODS

Male 4-week-old outbred CD-1 mice were fed an HFD to induce a polygenic model of human T2D. Adiponectin expression was examined in mouse pancreas by quantitative real-time polymerase chain reaction (qPCR), western blots and immunofluorescence analyses. Human umbilical vein endothelium cells (HUVECs) were transfected with an adiponectin-expressing lentivirus to determine the effect of adiponectin on angiogenic function in vitro.

RESULTS

Feeding mice an HFD for 9weeks resulted in constant hyperglycaemia, obesity, impaired glucose tolerance and insulin resistance. Additional hyperinsulinaemia emerged in mice fed an HFD for 18weeks. Interestingly, aberrant expression of adiponectin was detectable in the pancreatic vascular endothelial cells (VECs) of mice fed with an HFD, but not in mice fed with regular chow (RC). Expression levels of pancreatic adiponectin varied during the development of T2D. This extraordinary expression of adiponectin in pancreatic VECs played a role in protecting endothelial function against potential damage by HFD. Our in vitro study has demonstrated that adiponectin promotes angiogenic function.

CONCLUSION

These results reveal for the first time that adiponectin is expressed in pancreatic VECs of HFD-fed mice during the development of T2D as a protective adaptation in response to the HFD.

摘要

目的

已有研究报道,高脂肪饮食(HFD)喂养的大鼠骨骼肌和脂肪组织中的脂联素水平与胰岛素抵抗有关。我们的目的是探索脂联素是否也存在于胰腺中,以及在近交 CD-1 小鼠 2 型糖尿病(T2D)的发展过程中它可能发挥什么作用。

方法

4 周龄雄性近交 CD-1 小鼠给予 HFD 喂养,以诱导人类 T2D 的多基因模型。通过定量实时聚合酶链反应(qPCR)、western blot 和免疫荧光分析检测小鼠胰腺中的脂联素表达。用表达脂联素的慢病毒转染人脐静脉内皮细胞(HUVECs),以确定脂联素对体外血管生成功能的影响。

结果

用 HFD 喂养小鼠 9 周导致持续的高血糖、肥胖、葡萄糖耐量受损和胰岛素抵抗。用 HFD 喂养 18 周的小鼠还出现了高胰岛素血症。有趣的是,在 HFD 喂养的小鼠的胰腺血管内皮细胞(VECs)中可检测到脂联素的异常表达,但在常规饲料(RC)喂养的小鼠中则没有。在 T2D 的发展过程中,胰腺脂联素的表达水平发生变化。这种在胰腺 VECs 中脂联素的特殊表达在保护内皮功能免受 HFD 潜在损害方面发挥了作用。我们的体外研究表明,脂联素可促进血管生成功能。

结论

这些结果首次揭示,在 HFD 喂养的 T2D 发展过程中,脂联素作为对 HFD 的一种保护适应性,在胰腺 VECs 中表达。

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