ACE2/Ang-(1-7)改善肝细胞糖代谢

doi:10.3969/j.issn.1006-7795.2014.06.015

首都医科大学学报 ›› 2014, Vol. 35 ›› Issue (6): 755-759.doi: 10.3969/j.issn.1006-7795.2014.06.015

• 分子细胞内分泌代谢论坛 • 上一篇下一篇

ACE2/Ang-(1-7)改善肝细胞糖代谢

曹曦^1,2, 杨芳远^1,2, 史婷婷¹, 谢荣荣^1,2, 信中¹, 杨金奎^1,2

1. 首都医科大学附属北京同仁医院内分泌科, 北京 100730;
2. 糖尿病防治研究北京市重点实验室, 北京 100730

收稿日期:2014-11-06 发布日期:2014-12-15
通讯作者: 杨金奎 E-mail:jinkui.yang@gmail.com
基金资助:
国家自然科学基金(81200641, 81270918),北京市自然科学基金(7122040, 7131005)

ACE2/ Ang-(1-7) improves glucose metabolism in HepG2 cells

Cao Xi^1,2, Yang Fangyuan^1,2, Shi Tingting¹, Xie Rongrong^1,2, Xin Zhong¹, Yang Jinkui^1,2

1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
2. Beijng Key Laboratory of Diabetes Research and Care, Beijing 100730, China

Received:2014-11-06 Published:2014-12-15
Supported by:
This study was supported by National Natural Science Foundation of China(81200641, 81270918) and Natural Science Foundation of Beijing(7122040, 7131005).

摘要/Abstract

摘要：

目的肾素-血管紧张素系统(rennin-angiotensin system,RAS)参与糖代谢。血管紧张素转换酶2(angiotensin converting enzyme 2,ACE2)-血管紧张素(1-7)〔Ang-(1-7)〕-Ang-(1-7)受体(MAS)是新发现的RAS调节轴,可拮抗经典轴的生物效应。本文研究ACE2/Ang-(1-7)在肝脏糖代谢中的作用。方法 ① 利用Ang-(1-7)及MAS拮抗剂(A779)干预HepG2细胞,或ACE2过表达载体转染人肝细胞株HepG2;② 实时荧光定量PCR(real-time PCR,RT-PCR)检测糖代谢相关基因和氧化应激相关基因表达;③ 流式细胞仪检测活性氧(reactive oxygen species,ROS)浓度;④ 蛋白质印迹(Western blotting)法检测还原型辅酶II(NADPH)相关亚基的表达。结果 ① ACE2过表达细胞中,糖异生相关基因磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase,PEPCK)的表达水平显著降低,而葡萄糖-6-磷酸激酶(glucose-6-phosphatase,G6Pase)与对照组相比差异无统计学意义;② 葡萄糖转运蛋白2(glucose transporter type 2,Glut2)、胰岛素受体底物2(insulin receptor substrate,IRS-2)和腺苷酸活化蛋白激酶α亚基2〔adenosine 5'-monophosphate(AMP)-activated protein kinase,AMPKα2〕的表达水平显著增高,而细胞因子信号抑制因子-3(suppressor of cytokine signaling-3,SOCS-3)与对照组相比,表达量显著降低;③ Ang-(1-7)降低HepG2细胞内和细胞外ROS的浓度;④ Ang-(1-7)降低NADPH亚基p67和p22的表达;ACE2过表达,也能显著降低HepG2细胞中p22和p47的表达,同时,ACE2对氧化应激的保护作用能被A779抑制。结论 ACE2改善肝脏糖代谢,其机制可能与ACE2/Ang-(1-7)对肝脏氧化应激的保护作用有关。

关键词: 胰岛素抵抗, 肾素血管紧张素系统, 血管紧张素转换酶2, 氧化应激

Abstract:

Objective Renin angiotensin system(RAS) is involved in glucose metabolism. This study evaluated the effect of the new pathway of RAS, ACE2/Ang-(1-7), on glucose metabolism in hepatic cells. Methods ① HepG2 cells were treated with Ang-(1-7) or A779, or transfected with ACE2 over expression plasmid DNA; ② The expression of PEPCK, G6Pase, Glut2, IRS-2, AMPKα2, SOCS-3, p22 and p67 were detected by RT-PCR; ③ ROS was measured by DHE; ④ Western blotting was used to study p22 and p67. Results ① In ACE2-overexpressing HepG2 cells, the expression of PEPCK was decreased; ② SOCS-3 was decreased, while Glut2, IRS-2 and AMPKα2 were increased significantly; ③ Ang-(1-7) reduces ROS production; ④ Ang-(1-7) depressed the expression of p22 and p67 in HepG2 cells, and ACE2 inhibited relative protein expression levels of p47^phox and p22^phox. Conclusion ACE2/Ang-(1-7) could be involved in improving glucose metabolism via anti-oxidative effects.

Key words: insulin resistance, rennin-angiotensin system, angiotensin-converting enzyme 2, oxidative stress

中图分类号:

R589

曹曦, 杨芳远, 史婷婷, 谢荣荣, 信中, 杨金奎. ACE2/Ang-(1-7)改善肝细胞糖代谢[J]. 首都医科大学学报, 2014, 35(6): 755-759.

Cao Xi, Yang Fangyuan, Shi Tingting, Xie Rongrong, Xin Zhong, Yang Jinkui. ACE2/ Ang-(1-7) improves glucose metabolism in HepG2 cells[J]. Journal of Capital Medical University, 2014, 35(6): 755-759.

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ACE2/Ang-(1-7)改善肝细胞糖代谢

ACE2/ Ang-(1-7) improves glucose metabolism in HepG2 cells

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