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


  • S.H.S. Santos
  • J.F. Giani
  • V. Burghi
  • J.G. Miquet
  • F. Qadri
  • J.F. Braga
  • M. Todiras
  • K. Kotnik
  • N. Alenina
  • F.P. Dominici
  • R.A.S. Santos
  • M. Bader


  • Journal of Molecular Medicine


  • J Mol Med 92 (3): 255-265


  • 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.