The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver

Autores
Dominici, Fernando Pablo; Argentino, Danila Paula; Bartke, Andrzej; Turyn, Daniel
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The in vivo status of the proximal components of the insulin signaling system was investigated in skeletal muscle of Ames (Prop1 df/Prop1df) dwarf mice. The insulin-stimulated phosphorylation of the insulin receptor (IR) was reduced by 55% in Ames dwarf mice, while IR receptor protein content was not altered. Insulin-stimulated phosphorylation of IRS-1 and IRS-2 were decreased by 79 and 51%, respectively, while IRS-1 and IRS-2 protein levels were decreased by 66 and 43%. In addition, insulin-stimulated association of IRS-1 and IRS-2 with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase was significantly reduced (by 80 and 41%, respectively), whereas insulin-stimulated PI 3-kinase activity was reduced by 66%. However, insulin-stimulated phosphorylation of Akt was slightly reduced (by 20%), suggesting that the attenuation of insulin signaling downstream PI 3-kinase may involve other signaling molecules. Our current results demonstrate that the Prop1 mutation decreases high dose insulin responses in skeletal muscle. This alteration is remarkable because these animals are hypersensitive to insulin and display an augmented response to insulin in liver at the same signaling steps. Reduced response to insulin in skeletal muscle could be important for the control of glucose homeostasis in these animals and could have implications in their extended longevity.
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
Fil: Argentino, Danila Paula. 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
Fil: Bartke, Andrzej. University of Illinois; Estados Unidos
Fil: Turyn, Daniel. 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
Materia
AGING
GROWTH HORMONE
INSULIN RECEPTOR SUBSTRATE
INSULIN SENSITIVITY
INSULIN SIGNALING
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:11336/152125
Acceder
id CONICETDig_a9117042ff0b136b234232978f519284
oai_identifier_str oai:ri.conicet.gov.ar:11336/152125
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liverDominici, Fernando PabloArgentino, Danila PaulaBartke, AndrzejTuryn, DanielAGINGGROWTH HORMONEINSULIN RECEPTOR SUBSTRATEINSULIN SENSITIVITYINSULIN SIGNALINGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The in vivo status of the proximal components of the insulin signaling system was investigated in skeletal muscle of Ames (Prop1 df/Prop1df) dwarf mice. The insulin-stimulated phosphorylation of the insulin receptor (IR) was reduced by 55% in Ames dwarf mice, while IR receptor protein content was not altered. Insulin-stimulated phosphorylation of IRS-1 and IRS-2 were decreased by 79 and 51%, respectively, while IRS-1 and IRS-2 protein levels were decreased by 66 and 43%. In addition, insulin-stimulated association of IRS-1 and IRS-2 with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase was significantly reduced (by 80 and 41%, respectively), whereas insulin-stimulated PI 3-kinase activity was reduced by 66%. However, insulin-stimulated phosphorylation of Akt was slightly reduced (by 20%), suggesting that the attenuation of insulin signaling downstream PI 3-kinase may involve other signaling molecules. Our current results demonstrate that the Prop1 mutation decreases high dose insulin responses in skeletal muscle. This alteration is remarkable because these animals are hypersensitive to insulin and display an augmented response to insulin in liver at the same signaling steps. Reduced response to insulin in skeletal muscle could be important for the control of glucose homeostasis in these animals and could have implications in their extended longevity.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; ArgentinaFil: Argentino, Danila Paula. 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; ArgentinaFil: Bartke, Andrzej. University of Illinois; Estados UnidosFil: Turyn, Daniel. 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; ArgentinaElsevier Ireland2003-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/152125Dominici, Fernando Pablo; Argentino, Danila Paula; Bartke, Andrzej; Turyn, Daniel; The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver; Elsevier Ireland; Mechanisms of Ageing and Development; 124; 7; 7-2003; 819-8270047-6374CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/s0047-6374(03)00136-2info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0047637403001362info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:36Zoai:ri.conicet.gov.ar:11336/152125instacron: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:34982025-09-03 09:55:36.35CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver
title The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver
spellingShingle The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver
Dominici, Fernando Pablo
AGING
GROWTH HORMONE
INSULIN RECEPTOR SUBSTRATE
INSULIN SENSITIVITY
INSULIN SIGNALING
title_short The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver
title_full The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver
title_fullStr The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver
title_full_unstemmed The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver
title_sort The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver
dc.creator.none.fl_str_mv Dominici, Fernando Pablo
Argentino, Danila Paula
Bartke, Andrzej
Turyn, Daniel
author Dominici, Fernando Pablo
author_facet Dominici, Fernando Pablo
Argentino, Danila Paula
Bartke, Andrzej
Turyn, Daniel
author_role author
author2 Argentino, Danila Paula
Bartke, Andrzej
Turyn, Daniel
author2_role author
author
author
dc.subject.none.fl_str_mv AGING
GROWTH HORMONE
INSULIN RECEPTOR SUBSTRATE
INSULIN SENSITIVITY
INSULIN SIGNALING
topic AGING
GROWTH HORMONE
INSULIN RECEPTOR SUBSTRATE
INSULIN SENSITIVITY
INSULIN SIGNALING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The in vivo status of the proximal components of the insulin signaling system was investigated in skeletal muscle of Ames (Prop1 df/Prop1df) dwarf mice. The insulin-stimulated phosphorylation of the insulin receptor (IR) was reduced by 55% in Ames dwarf mice, while IR receptor protein content was not altered. Insulin-stimulated phosphorylation of IRS-1 and IRS-2 were decreased by 79 and 51%, respectively, while IRS-1 and IRS-2 protein levels were decreased by 66 and 43%. In addition, insulin-stimulated association of IRS-1 and IRS-2 with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase was significantly reduced (by 80 and 41%, respectively), whereas insulin-stimulated PI 3-kinase activity was reduced by 66%. However, insulin-stimulated phosphorylation of Akt was slightly reduced (by 20%), suggesting that the attenuation of insulin signaling downstream PI 3-kinase may involve other signaling molecules. Our current results demonstrate that the Prop1 mutation decreases high dose insulin responses in skeletal muscle. This alteration is remarkable because these animals are hypersensitive to insulin and display an augmented response to insulin in liver at the same signaling steps. Reduced response to insulin in skeletal muscle could be important for the control of glucose homeostasis in these animals and could have implications in their extended longevity.
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
Fil: Argentino, Danila Paula. 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
Fil: Bartke, Andrzej. University of Illinois; Estados Unidos
Fil: Turyn, Daniel. 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
description The in vivo status of the proximal components of the insulin signaling system was investigated in skeletal muscle of Ames (Prop1 df/Prop1df) dwarf mice. The insulin-stimulated phosphorylation of the insulin receptor (IR) was reduced by 55% in Ames dwarf mice, while IR receptor protein content was not altered. Insulin-stimulated phosphorylation of IRS-1 and IRS-2 were decreased by 79 and 51%, respectively, while IRS-1 and IRS-2 protein levels were decreased by 66 and 43%. In addition, insulin-stimulated association of IRS-1 and IRS-2 with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase was significantly reduced (by 80 and 41%, respectively), whereas insulin-stimulated PI 3-kinase activity was reduced by 66%. However, insulin-stimulated phosphorylation of Akt was slightly reduced (by 20%), suggesting that the attenuation of insulin signaling downstream PI 3-kinase may involve other signaling molecules. Our current results demonstrate that the Prop1 mutation decreases high dose insulin responses in skeletal muscle. This alteration is remarkable because these animals are hypersensitive to insulin and display an augmented response to insulin in liver at the same signaling steps. Reduced response to insulin in skeletal muscle could be important for the control of glucose homeostasis in these animals and could have implications in their extended longevity.
publishDate 2003
dc.date.none.fl_str_mv 2003-07
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/11336/152125
Dominici, Fernando Pablo; Argentino, Danila Paula; Bartke, Andrzej; Turyn, Daniel; The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver; Elsevier Ireland; Mechanisms of Ageing and Development; 124; 7; 7-2003; 819-827
0047-6374
CONICET Digital
CONICET
url http://hdl.handle.net/11336/152125
identifier_str_mv Dominici, Fernando Pablo; Argentino, Danila Paula; Bartke, Andrzej; Turyn, Daniel; The dwarf mutation decreases high dose insulin responses in skeletal muscle, the opposite of effects in liver; Elsevier Ireland; Mechanisms of Ageing and Development; 124; 7; 7-2003; 819-827
0047-6374
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/s0047-6374(03)00136-2
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0047637403001362
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
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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
_version_ 1842269354594402304
score 13.13397

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