Ang(1-7) treatment attenuates beta-cell dysfunction by improving pancreatic microcirculation in a rat model of Type 2 diabetes

摘要

Aims: Pancreatic microcirculation plays a pivotal role in the physiological function and survival of beta-cells. Ang(17) is a novel component of the renin angiotensin system (RAS) that has beneficial effects on microcirculation. In the present study, we investigated the effects of systemic Ang(1-7) administration (with or without its receptor Mas antagonist A779) on pancreatic microcirculation and beta-cell function. Methods: These effects were studied in vivo using a rat model of Type 2 diabetes (T2DM). Pancreatic microcirculation and islet microvessel density were measured; and beta-cell function, insulin content, and the apoptosis of islet cells were assessed, respectively. Additionally, we evaluated endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) concentration in islets. Results: After Ang(1-7) intervention, pancreatic microcirculation and intra-islet microvessel density were significantly improved (p < 0.05), and more importantly, first-phase insulin secretion of beta-cells as well as relative insulin content in islets were increased, and the amount of apoptotic islet cells was decreased (p < 0.05). And eNOS expression and NO release were up-regulated in pancreatic islets by Ang(1-7) administration (p < 0.05). These positive effects of Ang(1-7) were prevented by the addition of A-779 (p < 0.05). Conclusions: Our findings suggest that systemic Ang(1-7) treatment could attenuate beta-cell dysfunction and ameliorate islet cell apoptosis in T2DM rats by improving pancreatic microcirculation, perhaps through the mechanism of endothelial vasodilation. (C) 2013, Editrice Kurtis