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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.; Bader, M. "Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats" (2014) Journal of Molecular Medicine. 92(3):255-265
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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- β-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 μg/kg, reversed the established hyperglycemic state at a dose of 100 μg/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. Key message: A novel rat model with inducible diabetes can be used to evaluate new therapies. Angiotensin-(1-7) is effective in an oral formulation packaged in cyclodextrine. Angiotensin-(1-7) is a promising antidiabetic drug. © 2013 Springer-Verlag Berlin Heidelberg.

Registro:

Documento: Artículo
Título:Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats
Autor: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.; Bader, M.
Filiación:Department of Physiology and Biophysics, Biological Sciences Institute (ICB), Federal University of Minas Gerais (UFMG), Av Antonio Carlos 6627-ICB, 31270-901 Belo Horizonte MG, Brazil
Instituto de Química y Fisicoquímica Biológicas, Departamento de Química Biológica, Universidad de Buenos Aires, Junín 956, (1113) Buenos Aires, Argentina
Max-Delbrück-Center for Molecular Medicine (MDC), Buch, 13125 Berlin, Germany
Palabras clave:Angiotensin-(1-7); Antidiabetic; Diabetes; RNA interference; 2 hydroxypropyl beta cyclodextrin; angiotensin[1-7]; glucose; glucose transporter 4; glycogen synthase kinase 3beta; insulin; insulin receptor; insulin receptor substrate 1; protein kinase B; animal cell; animal cell culture; animal experiment; animal model; animal tissue; antidiabetic activity; article; body weight; cell isolation; cell membrane; controlled study; diabetic nephropathy; diuresis; down regulation; drug formulation; enzyme phosphorylation; glucose blood level; glucose transport; heart muscle cell; histology; hyperglycemia; immunoblotting; in vitro study; insulin blood level; insulin resistance; insulin sensitivity; long term care; male; newborn; non insulin dependent diabetes mellitus; nonhuman; prevention study; rat; signal transduction; therapy effect; urine volume; Administration, Oral; Angiotensin I; Animals; Animals, Newborn; Deoxyglucose; Diabetes Mellitus, Type 2; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Myocytes, Cardiac; Peptide Fragments; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction
Año:2014
Volumen:92
Número:3
Página de inicio:255
Página de fin:265
DOI: http://dx.doi.org/10.1007/s00109-013-1087-0
Título revista:Journal of Molecular Medicine
Título revista abreviado:J. Mol. Med.
ISSN:09462716
CODEN:JMLME
CAS:2 hydroxypropyl beta cyclodextrin, 94035-02-6; angiotensin[1-7], 39386-80-6; glucose, 50-99-7, 84778-64-3; glucose transporter 4, 188071-24-1; insulin, 9004-10-8; insulin receptor substrate 1, 175335-32-7; protein kinase B, 148640-14-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09462716_v92_n3_p255_Santos

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Citas:

---------- APA ----------
Santos, S.H.S., Giani, J.F., Burghi, V., Miquet, J.G., Qadri, F., Braga, J.F., Todiras, M.,..., Bader, M. (2014) . Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats. Journal of Molecular Medicine, 92(3), 255-265.
http://dx.doi.org/10.1007/s00109-013-1087-0
---------- CHICAGO ----------
Santos, S.H.S., Giani, J.F., Burghi, V., Miquet, J.G., Qadri, F., Braga, J.F., et al. "Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats" . Journal of Molecular Medicine 92, no. 3 (2014) : 255-265.
http://dx.doi.org/10.1007/s00109-013-1087-0
---------- MLA ----------
Santos, S.H.S., Giani, J.F., Burghi, V., Miquet, J.G., Qadri, F., Braga, J.F., et al. "Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats" . Journal of Molecular Medicine, vol. 92, no. 3, 2014, pp. 255-265.
http://dx.doi.org/10.1007/s00109-013-1087-0
---------- VANCOUVER ----------
Santos, S.H.S., Giani, J.F., Burghi, V., Miquet, J.G., Qadri, F., Braga, J.F., et al. Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats. J. Mol. Med. 2014;92(3):255-265.
http://dx.doi.org/10.1007/s00109-013-1087-0