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

doi:10.3969/j.issn.1006-7795.2014.06.015

Abstract

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

CLC Number:

R589

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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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2014.06.015

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2014/V35/I6/755

References

[1] Henriksen E J. Improvement of insulin sensitivity by antagonism of the renin-angiotensin system[J]. Am J Physiol Regul Integr Comp Physiol, 2007,293(3):R974-R980.
[2] Perkins J M, Davis S N. The renin-angiotensin-aldosterone system: a pivotal role in insulin sensitivity and glycemic control[J]. Curr Opin Endocrinol Diabetes Obes, 2008,15 (2):147-152.
[3] Santos S H, Giani J F, Burghi V, et al. Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats[J]. J Mol Med(Berl), 2014,92(3):255-265.
[4] Santos S H, Braga J F, Mario E G, et al. Improved lipid and glucose metabolism in transgenic rats with increased circulating angiotensin-(1-7)[J]. Arterioscler Thromb Vasc Biol, 2010,30(5):953-961.
[5] Paizis G, Tikellis C, Cooper M E, et al. Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2[J]. Gut, 2005,54(12):1790-1796.
[6] Taniguchi C M, Ueki K, Kahn R. Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism[J]. J Clin Invest, 2005,115(3):718-727.
[7] Richey J M, Ader M, Moore D, et al. Angiotensin Ⅱ induces insulin resistance independent of changes in interstitial insulin[J]. Am J Physiol, 1999,277(5 Pt 1):E920-E926.
[8] 崔常清.胰岛素抵抗的机制与临床研究进展[J].中国煤炭工业医学杂志,2012,(7) :1119-1121.
[9] Santos S H, Fernandes L R, Mario E G, et al. Mas deficiency in FVB/N mice produces marked changes in lipid and glycemic metabolism[J]. Diabetes, 2008,57(2):340-347.
[10] Clarke N E, Turner A J. Angiotensin-converting enzyme 2: the first decade[J]. Int J Hypertens, 2012,2012:307315.
[11] Tikellis C, Wookey P J, Candido R, et al. Improved islet morphology after blockade of the renin-angiotensin system in the ZDF rat[J]. Diabetes, 2004,53(4):989-997.
[12] Takeda M, Yamamoto K, Takemura Y, et al. Loss of ACE2 exaggerates high-calorie diet-induced insulin resistance by reduction of GLUT4 in mice[J]. Diabetes, 2013,62(1):223-233.
[13] Bedard K, Krause K H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology[J]. Physiol Rev, 2007,87(1):245-313.
[14] Wei Y, Sowers J R, Nistala R, et al. Angiotensin Ⅱ-induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells[J]. J Biol Chem, 2006,281(46):35137-35146.
[15] 臧莎莎,宋桉,宋光耀.骨骼肌胰岛素抵抗影响因素研究[J].解放军医药杂志,2013,(11):99-101.
[16] Yuan L, Li X, Li J, et al. Effects of renin-angiotensin system blockade on the islet morphology and function in rats with long-term high-fat diet[J]. Acta Diabetol, 2013,50(4):479-488.
[17] Hardie D G. The AMP-activated protein kinase pathway new players upstream and downstream[J]. J Cell Sci, 2004,117(Pt 23):5479-5487.
[18] Long Y C, Zierath J R. AMP-activated protein kinase signaling in metabolic regulation[J]. J Clin Invest, 2006,116(7):1776-1783.
[19] Nakamaru K, Matsumoto K, Taguchi T, et al. AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells[J]. Biochem Biophys Res Commun, 2005,328(2):449-454.
[20] Rui L, Yuan M, Frantz D, et al. SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2[J]. J Biol Chem, 2002,277(44):42394-42398.
[21] Senn J J, Klover P J, Nowak I A, et al. Suppressor of cytokine signaling-3(SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes[J]. J Biol Chem, 2003,278(16):13740-13746.