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

Acta Diabetol. 2012 Aug;49(4):291-9. doi: 10.1007/s00592-011-0348-z. Epub 2011 Nov 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Adiponectin / genetics
  • Angiotensin I / pharmacology*
  • Animals
  • Cells, Cultured
  • Gene Expression / drug effects
  • Glucose / metabolism*
  • Insulin Resistance
  • Male
  • Mice
  • NADPH Oxidases / genetics
  • Oxidative Stress / drug effects*
  • Peptide Fragments / pharmacology*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / drug effects*
  • Proto-Oncogene Proteins / physiology*
  • RNA, Messenger / analysis
  • Reactive Oxygen Species / metabolism
  • Receptors, G-Protein-Coupled / drug effects*
  • Receptors, G-Protein-Coupled / physiology*


  • Adiponectin
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • Receptors, G-Protein-Coupled
  • Angiotensin I
  • NADPH Oxidases
  • angiotensin I (1-7)
  • Glucose