Neurolysin Knockout Mice Generation and Initial Phenotype Characterization
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/37787 http://dx.doi.org/10.1074/jbc.M113.539148 |
Resumo: | The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln KO mice have increased glucose tolerance, insulin sensitivity, and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semiquantitative peptidomic analysis suggests an increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity. |
id |
UFSP_70f7b3175ecfba66fed6053266dde50b |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/37787 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Cavalcanti, Diogo M. L. P.Castro, Leandro M. [UNIFESP]Rosa Neto, José Cesar [UNIFESP]Seelaender, MariliaNeves, Rodrigo X.Oliveira, Vitor [UNIFESP]Forti, Fabio L.Iwai, Leo K.Gozzo, Fabio C.Todiras, MihailSchadock, InesBarros, Carlos C.Bader, Michael [UNIFESP]Ferro, Emer Suavinho [UNIFESP]Universidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Butantan InstUniversidade Estadual de Campinas (UNICAMP)Max Delbruck Ctr Mol MedUniv Fed Pelotas2016-01-24T14:37:19Z2016-01-24T14:37:19Z2014-05-30Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 289, n. 22, p. 15426-15440, 2014.0021-9258http://repositorio.unifesp.br/handle/11600/37787http://dx.doi.org/10.1074/jbc.M113.53914810.1074/jbc.M113.539148WOS:000337465400026The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln KO mice have increased glucose tolerance, insulin sensitivity, and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semiquantitative peptidomic analysis suggests an increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity.Brazilian National Research CouncilFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Pro-Reitoria de Pesquisa, University of São Paulo through Support Center for Research in Proteolysis and Cell Signaling ProcessBrazilian National Research Council Ph.D. FellowshipUniv São Paulo, Inst Biomed Sci, Dept Cell Biol & Dev, BR-05508900 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Pharmacol, Support Ctr Res Proteolysis & Cell Signaling, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04039032 São Paulo, BrazilUniv São Paulo, Inst Chem, Dept Biochem, Support Ctr Res Proteolysis & Cell Signaling, BR-05508000 São Paulo, BrazilButantan Inst, Special Lab Appl Toxinol, Ctr Toxins Immune Response & Cell Signaling, BR-05503000 São Paulo, BrazilUniv Estadual Campinas, Inst Chem, BR-13083862 Campinas, SP, BrazilMax Delbruck Ctr Mol Med, D-13125 Berlin, GermanyUniv Fed Pelotas, Dept Nutr, BR-96010610 Pelotas, RS, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04039032 São Paulo, BrazilBrazilian National Research Council: 559698/2009-7FAPESP: 04/04933-2Pro-Reitoria de Pesquisa, University of São Paulo through Support Center for Research in Proteolysis and Cell Signaling Process: 2012.1.17607.1.2Brazilian National Research Council Ph.D. Fellowship: GM/GD-140650/2010-5Brazilian National Research Council Ph.D. Fellowship: SWE-200678/2011-6Web of Science15426-15440engAmer Soc Biochemistry Molecular Biology IncJournal of Biological ChemistryGluconeogenesisGlucose MetabolismInsulinPeptidasesPeptidesIntracellular PeptidesOligopeptidaseNeurolysin Knockout Mice Generation and Initial Phenotype Characterizationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/377872022-11-04 14:18:41.001metadata only accessoai:repositorio.unifesp.br:11600/37787Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:28:28.193903Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Neurolysin Knockout Mice Generation and Initial Phenotype Characterization |
title |
Neurolysin Knockout Mice Generation and Initial Phenotype Characterization |
spellingShingle |
Neurolysin Knockout Mice Generation and Initial Phenotype Characterization Cavalcanti, Diogo M. L. P. Gluconeogenesis Glucose Metabolism Insulin Peptidases Peptides Intracellular Peptides Oligopeptidase |
title_short |
Neurolysin Knockout Mice Generation and Initial Phenotype Characterization |
title_full |
Neurolysin Knockout Mice Generation and Initial Phenotype Characterization |
title_fullStr |
Neurolysin Knockout Mice Generation and Initial Phenotype Characterization |
title_full_unstemmed |
Neurolysin Knockout Mice Generation and Initial Phenotype Characterization |
title_sort |
Neurolysin Knockout Mice Generation and Initial Phenotype Characterization |
author |
Cavalcanti, Diogo M. L. P. |
author_facet |
Cavalcanti, Diogo M. L. P. Castro, Leandro M. [UNIFESP] Rosa Neto, José Cesar [UNIFESP] Seelaender, Marilia Neves, Rodrigo X. Oliveira, Vitor [UNIFESP] Forti, Fabio L. Iwai, Leo K. Gozzo, Fabio C. Todiras, Mihail Schadock, Ines Barros, Carlos C. Bader, Michael [UNIFESP] Ferro, Emer Suavinho [UNIFESP] |
author_role |
author |
author2 |
Castro, Leandro M. [UNIFESP] Rosa Neto, José Cesar [UNIFESP] Seelaender, Marilia Neves, Rodrigo X. Oliveira, Vitor [UNIFESP] Forti, Fabio L. Iwai, Leo K. Gozzo, Fabio C. Todiras, Mihail Schadock, Ines Barros, Carlos C. Bader, Michael [UNIFESP] Ferro, Emer Suavinho [UNIFESP] |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) Butantan Inst Universidade Estadual de Campinas (UNICAMP) Max Delbruck Ctr Mol Med Univ Fed Pelotas |
dc.contributor.author.fl_str_mv |
Cavalcanti, Diogo M. L. P. Castro, Leandro M. [UNIFESP] Rosa Neto, José Cesar [UNIFESP] Seelaender, Marilia Neves, Rodrigo X. Oliveira, Vitor [UNIFESP] Forti, Fabio L. Iwai, Leo K. Gozzo, Fabio C. Todiras, Mihail Schadock, Ines Barros, Carlos C. Bader, Michael [UNIFESP] Ferro, Emer Suavinho [UNIFESP] |
dc.subject.eng.fl_str_mv |
Gluconeogenesis Glucose Metabolism Insulin Peptidases Peptides Intracellular Peptides Oligopeptidase |
topic |
Gluconeogenesis Glucose Metabolism Insulin Peptidases Peptides Intracellular Peptides Oligopeptidase |
description |
The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln KO mice have increased glucose tolerance, insulin sensitivity, and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semiquantitative peptidomic analysis suggests an increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-05-30 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:37:19Z |
dc.date.available.fl_str_mv |
2016-01-24T14:37:19Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 289, n. 22, p. 15426-15440, 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/37787 http://dx.doi.org/10.1074/jbc.M113.539148 |
dc.identifier.issn.none.fl_str_mv |
0021-9258 |
dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M113.539148 |
dc.identifier.wos.none.fl_str_mv |
WOS:000337465400026 |
identifier_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 289, n. 22, p. 15426-15440, 2014. 0021-9258 10.1074/jbc.M113.539148 WOS:000337465400026 |
url |
http://repositorio.unifesp.br/handle/11600/37787 http://dx.doi.org/10.1074/jbc.M113.539148 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Biological Chemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
15426-15440 |
dc.publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1783460295666040832 |