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

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.