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Angiotensin-(1-7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes

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Abstract

Although reactive oxygen species (ROS) contribute to glucose intolerance induced by the renin-angiotensin system (RAS) is well documented, the role of the newly discovered pathway of RAS, angiotensin (Ang)-(1-7)/Mas axis, in this process remains unknown. Here, we examined the effect of Ang-(1-7) on oxidative stress and glucose uptake in adipocytes. We used primary cultured epididymal adipocytes from C57 mice to study Ang-(1-7) effects on glucose uptake. We also treated fully differentiated 3T3-L1 adipocytes with exogenous Ang-(1-7) or overexpression of angiotensin-converting enzyme 2 (ACE2) to induce endogenous generation of Ang-(1-7) to clarify its effects on ROS production. Intracellular ROS was measured by flow cytometry, dihydroethidium (DHE), and nitroblue tetrazolium assay. Levels of NADPH oxidase and adiponectin mRNA were measured by real-time PCR. Ang-(1-7) improved glucose uptake both in basal and insulin-stimulated states. ROS production was slightly but significantly decreased in adipocytes treated with Ang-(1-7). Additionally, Mas receptor antagonist D-Ala7-Ang-(1-7) (A779) reversed the effect of Ang-(1-7) on glucose uptake and oxidative stress. Furthermore, treatment of adipocytes with Ang-(1-7) decreased NADPH oxidase mRNA levels. We also found that oxidative stress induced by glucose oxidase–suppressed expression of adiponectin, an insulin-sensitive protein. However, the suppression of oxidative stress by Ang-(1-7) restored adiponectin expression, while A779 agonists these changes induced by Ang-(1-7). In conclusion, Ang-(1-7) can protect against oxidative stress and improve glucose metabolism in adipocytes. These results show that Ang-(1-7) is a novel target for the improvement of glucose metabolism by preventing oxidative stress.

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Acknowledgments

This study was supported by grant No. 81070644, No. 30871187 and No. 30671001 from National Natural Science Foundation of China.

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There are no conflicts of interest.

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Authors and Affiliations

  1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Chang Liu, Xiao-Hong Lv, Hong-Xing Li, Xi Cao, Fen Zhang, Lei Wang, Mei Yu & Jin-Kui Yang

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  1. Chang Liu
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  2. Xiao-Hong Lv
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  4. Xi Cao
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  5. Fen Zhang
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Correspondence to Jin-Kui Yang.

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C. Liu and X.-H. Lv contributed equally to this paper.

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Liu, C., Lv, XH., Li, HX. et al. Angiotensin-(1-7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes. Acta Diabetol 49, 291–299 (2012). https://doi.org/10.1007/s00592-011-0348-z

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