Antioxidant effect of angiotensin (1-7) in the protection of pancreatic ß cell function

Zhang, Fen; Liu, Chang; Wang, Lei; Cao, Xi; Wang, Ying Ying; Yang, Jin Kui

by promoting β cell apoptosis and inactivating genes involved in insulin synthesis, such as v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog A and pancreatic and duodenal homeobox 1 (23) . In addition, hyperactivity of RAS leads to the development of β cell dysfunction by increasing oxidative stress and fibrosis (3) (4) . Ang (1-7) is considered to be an important antagonist of AngII and it has been shown to be able to reduce oxidative stress in the kidneys, cardiovascular system and neural system; however, the effects of Ang (1-7) in pancreatic β cell remains unknown. We hypothesized that the effects of Ang (1-7) occur via the same mechanisms in pancreatic β cells. As shown in the present study, Ang (1-7) reduced the intracellular ROS levels in INS-1 cells and had a protective effect on β cell function. Bindom et al (15) found that ACE2 overexpression in the pancreas of diabetic rats improves the function of β cells. Furthermore, the protective effect can be blocked by its specific inhibitor A779, which suggested that this effect was mediated by Ang (1-7) (15) and is consistent with the findings of the present study. In addition, chronic injection of Ang (1-7) improves insulin sensitivity in rats with a high-fructose diet (24) , Mas receptor knockout mice exhibited decreased insulin sensitivity, impaired glucose tolerance and glucose uptake (25) . These studies demonstrated the protective role of Ang (1) (2) (3) (4) (5) (6) (7) in the development of diabetes and metabolic syndrome. In addition, a number of studies in other systems supported the idea that the protective role of Ang (1-7) occurs by reducing oxidative stress. ACE2 overexpression results in a reduction of ROS formation in the brain (17) . Furthermore, continuous intravenous infusion of Ang (1-7) restores vasodilation and protects the myocardium via inhibition of oxidative stress (24) .