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Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats

Item Type:Article
Title:Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats
Creators Name:Santos, S.H.S., Giani, J.F., Burghi, V., Miquet, J.G., Qadri, F., Braga, J.F., Todiras, M., Kotnik, K., Alenina, N., Dominici, F.P., Santos, R.A.S. and Bader, M.
Abstract:Diabetes mellitus type 2 (DM2) is a disease with increasing importance in modern societies and insufficient treatment options. Pharmacological stimulation of insulin signaling, which is blunted in DM2, is a promising approach to treat this disease. It has been shown that activation of the angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system leads to an improved glucose uptake. In this study, we intended to evaluate, whether this effect could be exploited therapeutically. We first confirmed that Ang-(1-7) improves insulin signaling and glucose uptake in vitro in cultured cardiomyocytes. We then evaluated the therapeutic effect of a newly developed hydro-xypropyl-{beta}-cyclodextrin-based Ang-(1-7) nano-formulation in a novel transgenic rat model of inducible insulin resistance and DM2. The chronic administration of this compound prevented the marked elevation in blood glucose levels in these rats at a dose of 30 {mu}g/kg, reversed the established hyperglycemic state at a dose of 100 {mu}g/kg, and resulted in improved insulin sensitivity, reduced plasma insulin and decreased diabetic nephropathy. In conclusion, an oral Ang-(1-7) formulation reverses hyperglycemia and its consequences in an animal model of DM2 and represents a novel therapeutic option for the treatment of DM2 and other cardio-metabolic diseases.
Keywords:Diabetes, RNA Interference, Angiotensin-(1-7), Antidiabetic, Animals, Rats
Source:Journal of Molecular Medicine
Page Range:255-265
Date:March 2014
Official Publication:https://doi.org/10.1007/s00109-013-1087-0
PubMed:View item in PubMed

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