L Yuan1, Y Li, G Li, Y Song, X Gong. 1. Department of Endocrinology, Union Hospital, Tongji Medical College of HuaZhong Science & Technology University, 1277 Jiefang Road, Wuhan 430022, China. yuanli18cn@163.com.
Abstract
AIMS: Pancreatic microcirculation plays a pivotal role in the physiological function and survival of β-cells. Ang(1- 7) 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 A- 779) on pancreatic microcirculation and β-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 β-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 β-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 β-cell dysfunction and ameliorate islet cell apoptosis in T2DM rats by improving pancreatic microcirculation, perhaps through the mechanism of endothelial vasodilation.
AIMS: Pancreatic microcirculation plays a pivotal role in the physiological function and survival of β-cells. Ang(1- 7) 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 A- 779) on pancreatic microcirculation and β-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 β-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 β-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 β-cell dysfunction and ameliorate islet cell apoptosis in T2DM rats by improving pancreatic microcirculation, perhaps through the mechanism of endothelial vasodilation.
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