title: Angiotensin-(1-7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes.
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.
authors: Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
authors: Chang
authors: C
authors: Liu
authors: Xiao-Hong
authors: XH
authors: Lv
authors: Hong-Xing
authors: HX
authors: Li
authors: Xi
authors: X
authors: Cao
authors: Fen
authors: F
authors: Zhang
authors: Lei
authors: L
authors: Wang
authors: Mei
authors: M
authors: Yu
authors: Jin-Kui
authors: JK
authors: Yang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000502:physiology*
chemical_list: D052242:Adiponectin; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D019255:NADPH Oxidases; C118790:angiotensin I (1-7); D005947:Glucose