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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/85964
Acceder
id CONICETDig_9e7b6dde63447612e28297a181e7e62b
oai_identifier_str oai:ri.conicet.gov.ar:11336/85964
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:05:08Zoai: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:34982025-10-22 11:05:08.614CONICET 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/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv 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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