Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats
- Autores
- Santos, Sérgio H. S.; Giani, Jorge Fernando; Burghi, Valeria; Miquet, Johanna Gabriela; Qadri, Fatimunnisa; Braga, Janaina F.; Todiras, Mihail; Kotnik, Katarina; Alenina, Natalia; Dominici, Fernando Pablo; Santos, Robson A. S.; Bader, Michael
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Santos, Sérgio H. S.. Universidade Federal de Minas Gerais; Brasil
Fil: Giani, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Burghi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Miquet, Johanna Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Qadri, Fatimunnisa. Max-Delbrück-Center for Molecular Medicine; Alemania
Fil: Braga, Janaina F.. Universidade Federal de Minas Gerais; Brasil
Fil: Todiras, Mihail. Max-Delbrück-Center for Molecular Medicine; Alemania
Fil: Kotnik, Katarina. Max-Delbrück-Center for Molecular Medicine; Alemania
Fil: Alenina, Natalia. Max-Delbrück-Center for Molecular Medicine; Alemania
Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Santos, Robson A. S.. Universidade Federal de Minas Gerais; Brasil
Fil: Bader, Michael. Max-Delbrück-Center for Molecular Medicine; Alemania - Materia
-
ANGIOTENSIN-(1-7)
ANTIDIABETIC
DIABETES
RNA INTERFERENCE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/85964
Ver los metadatos del registro completo
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Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in ratsSantos, Sérgio H. S.Giani, Jorge FernandoBurghi, ValeriaMiquet, Johanna GabrielaQadri, FatimunnisaBraga, Janaina F.Todiras, MihailKotnik, KatarinaAlenina, NataliaDominici, Fernando PabloSantos, Robson A. S.Bader, MichaelANGIOTENSIN-(1-7)ANTIDIABETICDIABETESRNA INTERFERENCEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Diabetes 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.Fil: Santos, Sérgio H. S.. Universidade Federal de Minas Gerais; BrasilFil: Giani, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Burghi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Miquet, Johanna Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Qadri, Fatimunnisa. Max-Delbrück-Center for Molecular Medicine; AlemaniaFil: Braga, Janaina F.. Universidade Federal de Minas Gerais; BrasilFil: Todiras, Mihail. Max-Delbrück-Center for Molecular Medicine; AlemaniaFil: Kotnik, Katarina. Max-Delbrück-Center for Molecular Medicine; AlemaniaFil: Alenina, Natalia. Max-Delbrück-Center for Molecular Medicine; AlemaniaFil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Santos, Robson A. S.. Universidade Federal de Minas Gerais; BrasilFil: Bader, Michael. Max-Delbrück-Center for Molecular Medicine; AlemaniaSpringer2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85964Santos, Sérgio H. S.; Giani, Jorge Fernando; Burghi, Valeria; Miquet, Johanna Gabriela; Qadri, Fatimunnisa; et al.; Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats; Springer; Journal of Molecular Medicine (Berlin, Germany); 92; 3; 3-2014; 255-2650946-27161432-1440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00109-013-1087-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:59Zoai:ri.conicet.gov.ar:11336/85964instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:36:59.909CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
title |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
spellingShingle |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats Santos, Sérgio H. S. ANGIOTENSIN-(1-7) ANTIDIABETIC DIABETES RNA INTERFERENCE |
title_short |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
title_full |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
title_fullStr |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
title_full_unstemmed |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
title_sort |
Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats |
dc.creator.none.fl_str_mv |
Santos, Sérgio H. S. Giani, Jorge Fernando Burghi, Valeria Miquet, Johanna Gabriela Qadri, Fatimunnisa Braga, Janaina F. Todiras, Mihail Kotnik, Katarina Alenina, Natalia Dominici, Fernando Pablo Santos, Robson A. S. Bader, Michael |
author |
Santos, Sérgio H. S. |
author_facet |
Santos, Sérgio H. S. Giani, Jorge Fernando Burghi, Valeria Miquet, Johanna Gabriela Qadri, Fatimunnisa Braga, Janaina F. Todiras, Mihail Kotnik, Katarina Alenina, Natalia Dominici, Fernando Pablo Santos, Robson A. S. Bader, Michael |
author_role |
author |
author2 |
Giani, Jorge Fernando Burghi, Valeria Miquet, Johanna Gabriela Qadri, Fatimunnisa Braga, Janaina F. Todiras, Mihail Kotnik, Katarina Alenina, Natalia Dominici, Fernando Pablo Santos, Robson A. S. Bader, Michael |
author2_role |
author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
ANGIOTENSIN-(1-7) ANTIDIABETIC DIABETES RNA INTERFERENCE |
topic |
ANGIOTENSIN-(1-7) ANTIDIABETIC DIABETES RNA INTERFERENCE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
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. Fil: Santos, Sérgio H. S.. Universidade Federal de Minas Gerais; Brasil Fil: Giani, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina Fil: Burghi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina Fil: Miquet, Johanna Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina Fil: Qadri, Fatimunnisa. Max-Delbrück-Center for Molecular Medicine; Alemania Fil: Braga, Janaina F.. Universidade Federal de Minas Gerais; Brasil Fil: Todiras, Mihail. Max-Delbrück-Center for Molecular Medicine; Alemania Fil: Kotnik, Katarina. Max-Delbrück-Center for Molecular Medicine; Alemania Fil: Alenina, Natalia. Max-Delbrück-Center for Molecular Medicine; Alemania Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina Fil: Santos, Robson A. S.. Universidade Federal de Minas Gerais; Brasil Fil: Bader, Michael. Max-Delbrück-Center for Molecular Medicine; Alemania |
description |
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. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-03 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/85964 Santos, Sérgio H. S.; Giani, Jorge Fernando; Burghi, Valeria; Miquet, Johanna Gabriela; Qadri, Fatimunnisa; et al.; Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats; Springer; Journal of Molecular Medicine (Berlin, Germany); 92; 3; 3-2014; 255-265 0946-2716 1432-1440 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/85964 |
identifier_str_mv |
Santos, Sérgio H. S.; Giani, Jorge Fernando; Burghi, Valeria; Miquet, Johanna Gabriela; Qadri, Fatimunnisa; et al.; Oral administration of angiotensin-(1-7) ameliorates type 2 diabetes in rats; Springer; Journal of Molecular Medicine (Berlin, Germany); 92; 3; 3-2014; 255-265 0946-2716 1432-1440 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00109-013-1087-0 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.069144 |