Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.B1 (angiotensin-converting enzyme 2)
 1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Angiotensin-(1-7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes. 2204 30

In the classical renin angiotensin system (RAS), angiotensin II Ang IIplays many important roles in cardiovascular disease and in kidney, brain, and other organs via the Ang II type 1 receptor (AT1). The RAS consists of many angiotensin peptides, including Ang (1-7), Ang (1-9), Ang (2-8), and Ang IV. Ang (1-7), produced by angiotensin-converting enzyme 2 (ACE2), has received attention because ACE2-deficient mice have heart failure. In addition, the proto-oncogene mas and insulin regulatory aminopeptidase (IRAP) have been identified as receptors for Ang (1-7) and Ang IV, respectively, accelerating investigations into both peptides. Many groups have suggested that the ACE2/Ang (1-7)/mas axis results in beneficial effects in cardiovascular disease, renal damage, and glucose intolerance and plays an independent role in kidney disease and glucose metabolism. On the other hand, Ang IV/IRAP strongly influences memory disturbance and protects against brain ischemia. Finally, the classical RAS-ACE/Ang II/AT1 axis blockade yields beneficial effects in the context of organ damage, and additional modulation of ACE2/Ang (1-7)/mas or angiotensin IV/IRAP with this blockade results in even greater improvement. In the near future, new treatments targeting RAS and using new angiotensin peptide players might be developed for managing lifestyle-related diseases.
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PMID:Angiotensin (1-7) and other angiotensin peptides. 2317 20