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A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Published on: June 25, 2018
Antioxidant effect of angiotensin (1‑7) in the protection of pancreatic β cell function
Fen Zhang1, Chang Liu1, Lei Wang1
1Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China.
Abstract:
It is well known that the local renin-angiotensin system (RAS) is activated in the diabetic state, which results in an increase in the level of oxidative stress injury to pancreatic β cells. The angiotensin‑converting enzyme 2 (ACE2)/angiotensin (1‑7) [Ang (1‑7)]/Mas axis is a negative regulator of the classical renin‑angiotensin system. In order to investigate the antioxidant effect of Ang (1‑7) on pancreatic β cells, INS‑1 cells were cultured and oxidative stress was induced by treatment with H2O2. Glucose‑stimulated insulin secretion (GSIS), the generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and glucose-stimulated calcium (GSCa) responses in β cells were determined following treatment with Ang (1-7). It was observed that H2O2 significantly impaired the insulin secreting function, increased the production of ROS, and also decreased the levels of GSCa and MMP. Pre‑treatment with Ang (1‑7) alleviated these effects and treatment with A779 [antagonist of Ang (1‑7)] prevented the effects of Ang (1-7). Based on these findings, it was concluded that Ang (1‑7) can protect pancreatic β cells from oxidative injury and such protection can be blocked by its antagonist A779.
Insights
Angiotensin (1-7) protects pancreatic beta cells from oxidative stress, a key factor in diabetes. This protective effect, mediated by the ACE2/Ang (1-7)/Mas axis, was confirmed using cell models and reversed by an antagonist.
Area of Science:
- Endocrinology
- Cell Biology
- Diabetology
Background:
- The renin-angiotensin system (RAS) is activated in diabetes, increasing oxidative stress in pancreatic beta cells.
- The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang (1-7)]/Mas axis negatively regulates the classical RAS.
Purpose of the Study:
- To investigate the antioxidant effects of Ang (1-7) on pancreatic beta cells under oxidative stress conditions.
Main Methods:
- INS-1 cells were cultured and exposed to hydrogen peroxide (H2O2) to induce oxidative stress.
- Effects of Ang (1-7) on glucose-stimulated insulin secretion (GSIS), reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), and glucose-stimulated calcium (GSCa) responses were assessed.
- The role of the Ang (1-7) receptor was evaluated using its antagonist, A779.
Main Results:
- H2O2 impaired GSIS, increased ROS production, and decreased GSCa and MMP in beta cells.
- Pre-treatment with Ang (1-7) alleviated H2O2-induced damage.
- The protective effects of Ang (1-7) were blocked by the antagonist A779.
Conclusions:
- Ang (1-7) exhibits significant antioxidant effects, protecting pancreatic beta cells from oxidative injury.
- This protection is mediated through the ACE2/Ang (1-7)/Mas axis and can be inhibited by A779.
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