Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme

Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed metalloprotease that degrades insulin and several other intermediate-size peptides. For many decades, IDE had been assumed to be involved primarily in hepatic insulin clearance, a key process that regulates availability...

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Autores: González Casimiro, Carlos M., Merino, Beatriz, Casanueva-Álvarez, Elena, Postigo-Casado, Tamara, Cámara-Torres, Patricia, Fernández-Díez, Cristina, Leissring, Malcolm A., Cózar-Castellano, Irene, Perdomo, Germán
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/227918
Acceso en línea:http://hdl.handle.net/10261/227918
Access Level:acceso abierto
Palabra clave:Insulin-degrading enzyme
Insulin resistance
Pancreas
Liver
Insulin-receptor
Glucose transporters
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spelling Modulation of Insulin Sensitivity by Insulin-Degrading EnzymeGonzález Casimiro, Carlos M.Merino, BeatrizCasanueva-Álvarez, ElenaPostigo-Casado, TamaraCámara-Torres, PatriciaFernández-Díez, CristinaLeissring, Malcolm A.Cózar-Castellano, IrenePerdomo, GermánInsulin-degrading enzymeInsulin resistancePancreasLiverInsulin-receptorGlucose transportersInsulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed metalloprotease that degrades insulin and several other intermediate-size peptides. For many decades, IDE had been assumed to be involved primarily in hepatic insulin clearance, a key process that regulates availability of circulating insulin levels for peripheral tissues. Emerging evidence, however, suggests that IDE has several other important physiological functions relevant to glucose and insulin homeostasis, including the regulation of insulin secretion from pancreatic β-cells. Investigation of mice with tissue-specific genetic deletion of <i>Ide</i> in the liver and pancreatic β-cells (L-IDE-KO and B-IDE-KO mice, respectively) has revealed additional roles for IDE in the regulation of hepatic insulin action and sensitivity. In this review, we discuss current knowledge about IDE’s function as a regulator of insulin secretion and hepatic insulin sensitivity, both evaluating the classical view of IDE as an insulin protease and also exploring evidence for several non-proteolytic functions. Insulin proteostasis and insulin sensitivity have both been highlighted as targets controlling blood sugar levels in type 2 diabetes, so a clearer understanding the physiological functions of IDE in pancreas and liver could led to the development of novel therapeutics for the treatment of this disease.This research was funded by the Ministerio de Economía, Industria y Competitividad, grant numbers SAF2016-77871-C2-1-R to I.C.-C.; SAF2016-77871-C2-2-R to G.P.; Ministerio de Ciencia e Innovación PID2019-110496RB-C21 to I.C.-C.; PID2019-110496RB-C22 to G.P.; European Foundation for the Study of Diabetes (European Diabetes Research Programme on New Targets for Type 2 Diabetes supported by MSD-2017) to I.C.-C. and G.P.; and the US National Institutes of Health (GM115617) to M.A.L. The project leading to these results has received funding from “la Caixa” Foundation, under agreement LCF/PR/PR18/51130007 to G.P., C.M.G.-C. and E.C.-Á. were supported by fellowships from the Junta de Castilla y León and the European Social Fund (ORDER EDU/574/2018 and ORDER EDU/556/2019, respectively).Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionLa CaixaJunta de Castilla y LeónConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/227918reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-77871-C2-1-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-77871-C2-2-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110496RB-C21info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110496RB-C22Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2279182026-05-22T06:33:51Z
dc.title.none.fl_str_mv Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
title Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
spellingShingle Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
González Casimiro, Carlos M.
Insulin-degrading enzyme
Insulin resistance
Pancreas
Liver
Insulin-receptor
Glucose transporters
title_short Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
title_full Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
title_fullStr Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
title_full_unstemmed Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
title_sort Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme
dc.creator.none.fl_str_mv González Casimiro, Carlos M.
Merino, Beatriz
Casanueva-Álvarez, Elena
Postigo-Casado, Tamara
Cámara-Torres, Patricia
Fernández-Díez, Cristina
Leissring, Malcolm A.
Cózar-Castellano, Irene
Perdomo, Germán
author González Casimiro, Carlos M.
author_facet González Casimiro, Carlos M.
Merino, Beatriz
Casanueva-Álvarez, Elena
Postigo-Casado, Tamara
Cámara-Torres, Patricia
Fernández-Díez, Cristina
Leissring, Malcolm A.
Cózar-Castellano, Irene
Perdomo, Germán
author_role author
author2 Merino, Beatriz
Casanueva-Álvarez, Elena
Postigo-Casado, Tamara
Cámara-Torres, Patricia
Fernández-Díez, Cristina
Leissring, Malcolm A.
Cózar-Castellano, Irene
Perdomo, Germán
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
European Commission
La Caixa
Junta de Castilla y León
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Insulin-degrading enzyme
Insulin resistance
Pancreas
Liver
Insulin-receptor
Glucose transporters
topic Insulin-degrading enzyme
Insulin resistance
Pancreas
Liver
Insulin-receptor
Glucose transporters
description Insulin-degrading enzyme (IDE) is a highly conserved and ubiquitously expressed metalloprotease that degrades insulin and several other intermediate-size peptides. For many decades, IDE had been assumed to be involved primarily in hepatic insulin clearance, a key process that regulates availability of circulating insulin levels for peripheral tissues. Emerging evidence, however, suggests that IDE has several other important physiological functions relevant to glucose and insulin homeostasis, including the regulation of insulin secretion from pancreatic β-cells. Investigation of mice with tissue-specific genetic deletion of <i>Ide</i> in the liver and pancreatic β-cells (L-IDE-KO and B-IDE-KO mice, respectively) has revealed additional roles for IDE in the regulation of hepatic insulin action and sensitivity. In this review, we discuss current knowledge about IDE’s function as a regulator of insulin secretion and hepatic insulin sensitivity, both evaluating the classical view of IDE as an insulin protease and also exploring evidence for several non-proteolytic functions. Insulin proteostasis and insulin sensitivity have both been highlighted as targets controlling blood sugar levels in type 2 diabetes, so a clearer understanding the physiological functions of IDE in pancreas and liver could led to the development of novel therapeutics for the treatment of this disease.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/227918
url http://hdl.handle.net/10261/227918
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-77871-C2-1-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-77871-C2-2-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110496RB-C21
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110496RB-C22
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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