Targeting Insulin-Degrading Enzyme in Insulin Clearance

© 2021 by the authors.

Detalles Bibliográficos
Autores: Leissring, Malcolm A., González-Casimiro, Carlos M., Merino, Beatriz, Suire, Caitlin N., 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:10261/241744
Acceso en línea:http://hdl.handle.net/10261/241744
Access Level:acceso abierto
Palabra clave:Insulin-degrading enzyme
Insulin clearance
Liver
Pharmacological inhibitors
Insulin resistance
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spelling Targeting Insulin-Degrading Enzyme in Insulin ClearanceLeissring, Malcolm A.González-Casimiro, Carlos M.Merino, BeatrizSuire, Caitlin N.Perdomo, GermánInsulin-degrading enzymeInsulin clearanceLiverPharmacological inhibitorsInsulin resistance© 2021 by the authors.Hepatic insulin clearance, a physiological process that in response to nutritional cues clears ~50–80% of circulating insulin, is emerging as an important factor in our understanding of the pathogenesis of type 2 diabetes mellitus (T2DM). Insulin-degrading enzyme (IDE) is a highly conserved Zn2+-metalloprotease that degrades insulin and several other intermediate-size peptides. Both, insulin clearance and IDE activity are reduced in diabetic patients, albeit the cause-effect relationship in humans remains unproven. Because historically IDE has been proposed as the main enzyme involved in insulin degradation, efforts in the development of IDE inhibitors as therapeutics in diabetic patients has attracted attention during the last decades. In this review, we retrace the path from Mirsky’s seminal discovery of IDE to the present, highlighting the pros and cons of the development of IDE inhibitors as a pharmacological approach to treating diabetic patients.This research was funded by the Ministerio de Economía, Industria y Competitividad, grant number SAF2016-77871-C2-2-R to G.P.; Ministerio de Ciencia e Innovación 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 G.P.; European Foundation for the Study of Diabetes (EFSD) -Novo Nordisk to B.M.; 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. was supported by a fellowship from the Junta de Castilla y León and the European Social Fund (ORDER EDU/574/2018). B.M. was supported by a “Rising Star” fellowship (EFSD-Novo Nordisk).Multidisciplinary Digital Publishing InstituteMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)European Foundation for the Study of DiabetesNovo NordiskNational Institutes of Health (US)Fundación la CaixaJunta de Castilla y LeónConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/241744reponame: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#info: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-C22PID2019-110496RB-C22/AEI/10.13039/501100011033http://dx.doi.org/10.3390/ijms22052235Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2417442026-05-22T06:33:51Z
dc.title.none.fl_str_mv Targeting Insulin-Degrading Enzyme in Insulin Clearance
title Targeting Insulin-Degrading Enzyme in Insulin Clearance
spellingShingle Targeting Insulin-Degrading Enzyme in Insulin Clearance
Leissring, Malcolm A.
Insulin-degrading enzyme
Insulin clearance
Liver
Pharmacological inhibitors
Insulin resistance
title_short Targeting Insulin-Degrading Enzyme in Insulin Clearance
title_full Targeting Insulin-Degrading Enzyme in Insulin Clearance
title_fullStr Targeting Insulin-Degrading Enzyme in Insulin Clearance
title_full_unstemmed Targeting Insulin-Degrading Enzyme in Insulin Clearance
title_sort Targeting Insulin-Degrading Enzyme in Insulin Clearance
dc.creator.none.fl_str_mv Leissring, Malcolm A.
González-Casimiro, Carlos M.
Merino, Beatriz
Suire, Caitlin N.
Perdomo, Germán
author Leissring, Malcolm A.
author_facet Leissring, Malcolm A.
González-Casimiro, Carlos M.
Merino, Beatriz
Suire, Caitlin N.
Perdomo, Germán
author_role author
author2 González-Casimiro, Carlos M.
Merino, Beatriz
Suire, Caitlin N.
Perdomo, Germán
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Foundation for the Study of Diabetes
Novo Nordisk
National Institutes of Health (US)
Fundación 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 clearance
Liver
Pharmacological inhibitors
Insulin resistance
topic Insulin-degrading enzyme
Insulin clearance
Liver
Pharmacological inhibitors
Insulin resistance
description © 2021 by the authors.
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_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/241744
url http://hdl.handle.net/10261/241744
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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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-C22
PID2019-110496RB-C22/AEI/10.13039/501100011033
http://dx.doi.org/10.3390/ijms22052235
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
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