{"id":"https://openalex.org/W2037565549","doi":"https://doi.org/10.1210/mend-5-10-1467","title":"Regulation of Insulin Degradation: Expression of an Evolutionarily Conserved Insulin-Degrading Enzyme Increases Degradation via an Intracellular Pathway","display_name":"Regulation of Insulin Degradation: Expression of an Evolutionarily Conserved Insulin-Degrading Enzyme Increases Degradation via an Intracellular Pathway","publication_year":1991,"publication_date":"1991-10-01","ids":{"openalex":"https://openalex.org/W2037565549","doi":"https://doi.org/10.1210/mend-5-10-1467","mag":"2037565549","pmid":"https://pubmed.ncbi.nlm.nih.gov/1775131"},"language":"en","primary_location":{"id":"doi:10.1210/mend-5-10-1467","doi":"https://doi.org/10.1210/mend-5-10-1467","is_oa":true,"landing_page_url":"https://doi.org/10.1210/mend-5-10-1467","pdf_url":"https://academic.oup.com/mend/article-pdf/5/10/1467/10490314/mend1467.pdf","source":{"id":"https://openalex.org/S57449756","display_name":"Molecular Endocrinology","issn_l":"0888-8809","issn":["0888-8809","1944-9917"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-100"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Endocrinology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://academic.oup.com/mend/article-pdf/5/10/1467/10490314/mend1467.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5012520968","display_name":"Wen\u2010Liang Kuo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wen-Liang Kuo","raw_affiliation_strings":["Ben May Institute, Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Ben May Institute, Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5033876838","display_name":"Barry D. Gehm","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Barry D. Gehm","raw_affiliation_strings":["Ben May Institute, Department of Pharmacological and Physiological Sciences, University of Chicago Chicago, Illinois 60637"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Ben May Institute, Department of Pharmacological and Physiological Sciences, University of Chicago Chicago, Illinois 60637","institution_ids":["https://openalex.org/I40347166"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5035583989","display_name":"Marsha Rich Rosner","orcid":"https://orcid.org/0000-0001-6586-8335","observed_orcids":["https://orcid.org/0000-0001-6586-8335"]},"institutions":[{"id":"https://openalex.org/I40347166","display_name":"University of Chicago","ror":"https://ror.org/024mw5h28","country_code":"US","type":"education","lineage":["https://openalex.org/I40347166"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Marsha Rich Rosner","raw_affiliation_strings":["Ben May Institute, Department of Pharmacological and Physiological Sciences, University of Chicago Chicago, Illinois 60637"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Ben May Institute, Department of Pharmacological and Physiological Sciences, University of Chicago Chicago, Illinois 60637","institution_ids":["https://openalex.org/I40347166"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I40347166"],"apc_list":null,"apc_paid":null,"fwci":1.0128,"has_fulltext":true,"cited_by_count":42,"citation_normalized_percentile":{"value":0.74407757,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":96},"biblio":{"volume":"5","issue":"10","first_page":"1467","last_page":"1476"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11339","display_name":"Metabolism, Diabetes, and Cancer","score":0.4350999891757965,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11339","display_name":"Metabolism, Diabetes, and Cancer","score":0.4350999891757965,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10839","display_name":"Pancreatic function and diabetes","score":0.11959999799728394,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10620","display_name":"Protease and Inhibitor Mechanisms","score":0.10109999775886536,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/insulin-degrading-enzyme","display_name":"insulin-degrading enzyme","score":0.9980000257492065},{"id":"https://openalex.org/keywords/insulin-degradation","display_name":"insulin degradation","score":0.9800000190734863},{"id":"https://openalex.org/keywords/insulin-receptor-binding","display_name":"insulin receptor binding","score":0.75},{"id":"https://openalex.org/keywords/lysosomal-degradation","display_name":"lysosomal degradation","score":0.5730000138282776},{"id":"https://openalex.org/keywords/chloroquine","display_name":"chloroquine","score":0.8999999761581421},{"id":"https://openalex.org/keywords/ammonium-chloride","display_name":"ammonium chloride","score":0.7760000228881836}],"concepts":[{"id":"https://openalex.org/C2780331951","wikidata":"https://www.wikidata.org/wiki/Q1225690","display_name":"Insulin-degrading enzyme","level":3,"score":0.8857113122940063},{"id":"https://openalex.org/C2779306644","wikidata":"https://www.wikidata.org/wiki/Q2002370","display_name":"Insulin","level":2,"score":0.8270266056060791},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.7633785009384155},{"id":"https://openalex.org/C28406088","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Extracellular","level":2,"score":0.654240071773529},{"id":"https://openalex.org/C79879829","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Intracellular","level":2,"score":0.6376050114631653},{"id":"https://openalex.org/C54009773","wikidata":"https://www.wikidata.org/wiki/Q1429031","display_name":"Transfection","level":3,"score":0.5948271155357361},{"id":"https://openalex.org/C2779679103","wikidata":"https://www.wikidata.org/wiki/Q5251805","display_name":"Degradation (telecommunications)","level":2,"score":0.5401495695114136},{"id":"https://openalex.org/C112446052","wikidata":"https://www.wikidata.org/wiki/Q422579","display_name":"Insulin receptor","level":4,"score":0.535027027130127},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4675739109516144},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.37692031264305115},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.17274224758148193},{"id":"https://openalex.org/C2777391703","wikidata":"https://www.wikidata.org/wiki/Q1053470","display_name":"Insulin resistance","level":3,"score":0.1392948031425476},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.11468476057052612},{"id":"https://openalex.org/C76155785","wikidata":"https://www.wikidata.org/wiki/Q418","display_name":"Telecommunications","level":1,"score":0.0},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.0}],"mesh":[{"descriptor_ui":"D000643","descriptor_name":"Ammonium Chloride","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002738","descriptor_name":"Chloroquine","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D004330","descriptor_name":"Drosophila","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D005075","descriptor_name":"Biological Evolution","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007328","descriptor_name":"Insulin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D007339","descriptor_name":"Insulysin","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D007339","descriptor_name":"Insulysin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D007700","descriptor_name":"Kinetics","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008247","descriptor_name":"Lysosomes","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D010957","descriptor_name":"Plasmids","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011994","descriptor_name":"Recombinant Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D012689","descriptor_name":"Sequence Homology, Nucleic Acid","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014162","descriptor_name":"Transfection","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1210/mend-5-10-1467","doi":"https://doi.org/10.1210/mend-5-10-1467","is_oa":true,"landing_page_url":"https://doi.org/10.1210/mend-5-10-1467","pdf_url":"https://academic.oup.com/mend/article-pdf/5/10/1467/10490314/mend1467.pdf","source":{"id":"https://openalex.org/S57449756","display_name":"Molecular Endocrinology","issn_l":"0888-8809","issn":["0888-8809","1944-9917"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-100"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Endocrinology","raw_type":"journal-article"},{"id":"pmid:1775131","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/1775131","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular endocrinology (Baltimore, Md.)","raw_type":"Comparative Study"}],"best_oa_location":{"id":"doi:10.1210/mend-5-10-1467","doi":"https://doi.org/10.1210/mend-5-10-1467","is_oa":true,"landing_page_url":"https://doi.org/10.1210/mend-5-10-1467","pdf_url":"https://academic.oup.com/mend/article-pdf/5/10/1467/10490314/mend1467.pdf","source":{"id":"https://openalex.org/S57449756","display_name":"Molecular Endocrinology","issn_l":"0888-8809","issn":["0888-8809","1944-9917"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","poland-100"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Endocrinology","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320306089","display_name":"American Diabetes Association","ror":"https://ror.org/04f6cgz95"},{"id":"https://openalex.org/F4320308306","display_name":"Muscular Dystrophy Association","ror":"https://ror.org/01frxsf98"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2037565549.pdf","grobid_xml":"https://content.openalex.org/works/W2037565549.grobid-xml"},"referenced_works_count":31,"referenced_works":["https://openalex.org/W1483136265","https://openalex.org/W1488062553","https://openalex.org/W1503993378","https://openalex.org/W1516189034","https://openalex.org/W1550371002","https://openalex.org/W1573534810","https://openalex.org/W1587305227","https://openalex.org/W1967026655","https://openalex.org/W1971004360","https://openalex.org/W1973430331","https://openalex.org/W1992381167","https://openalex.org/W2008637706","https://openalex.org/W2014528878","https://openalex.org/W2038143756","https://openalex.org/W2040691151","https://openalex.org/W2041015024","https://openalex.org/W2045804978","https://openalex.org/W2045951664","https://openalex.org/W2062893462","https://openalex.org/W2074152855","https://openalex.org/W2077154346","https://openalex.org/W2096864633","https://openalex.org/W2113824517","https://openalex.org/W2120820030","https://openalex.org/W2128635872","https://openalex.org/W2129762414","https://openalex.org/W2144206181","https://openalex.org/W2144634347","https://openalex.org/W2147177696","https://openalex.org/W2396068173","https://openalex.org/W4323913119"],"related_works":["https://openalex.org/W172293654","https://openalex.org/W2000842689","https://openalex.org/W1982339815","https://openalex.org/W1480038774","https://openalex.org/W1920884358","https://openalex.org/W2138041386","https://openalex.org/W52314393","https://openalex.org/W2118314558","https://openalex.org/W2320153811","https://openalex.org/W2074152855"],"abstract_inverted_index":{"The":[0,60,159,204,235],"insulin-degrading":[1],"enzyme":[2,8],"(IDE)":[3],"is":[4,82],"an":[5,250],"evolutionarily":[6],"conserved":[7],"that":[9,115,194,224,238],"has":[10,69],"been":[11,30],"implicated":[12],"in":[13,24,47,66,85,94,106,124,174,199,215],"cellular":[14,119],"insulin":[15,26,45,77,120,153,167,182,216,231,245],"degradation,":[16],"but":[17],"its":[18,56],"site":[19,146],"of":[20,41,90,109,111,147,152,165,230,244],"action":[21],"and":[22,55,81,130,139,208,227],"importance":[23],"regulating":[25],"degradation":[27,46,110,164,175,217,232,243],"have":[28],"not":[29,132,211],"clearly":[31],"established.":[32],"We":[33],"addressed":[34],"this":[35],"question":[36],"by":[37,219,246],"examining":[38],"the":[39,107,125,135,145,150,202,213,225,242],"effects":[40],"overexpressing":[42],"IDE":[43,53,116,148,195,239],"on":[44],"COS":[48,95],"cells,":[49],"using":[50],"both":[51],"human":[52],"(hIDE)":[54],"Drosophila":[57],"homolog":[58],"(dIDE).":[59],"dIDE,":[61,222],"which":[62],"was":[63,127,157,176,183],"recently":[64],"cloned":[65],"our":[67],"laboratory,":[68],"46%":[70],"amino":[71],"acid":[72],"identity":[73],"with":[74,78,221],"hIDE,":[75],"degrades":[76],"comparable":[79],"efficiency,":[80],"readily":[83],"expressed":[84],"mammalian":[86],"cells.":[87,141,171],"Transient":[88],"expression":[89],"dIDE":[91],"or":[92,188],"hIDE":[93],"monkey":[96],"kidney":[97],"cells":[98,161,248],"led":[99],"to":[100,103,169,185],"a":[101],"5-":[102],"7-fold":[104],"increase":[105,173,214],"rate":[108],"extracellular":[112,189],"insulin,":[113],"indicating":[114,223],"can":[117,240],"regulate":[118,241],"degradation.":[121,190],"Insulin-degrading":[122],"activity":[123],"medium":[126],"very":[128],"low":[129],"could":[131],"account":[133],"for":[134],"difference":[136],"between":[137],"transfected":[138],"control":[140,170],"To":[142],"further":[143],"localize":[144],"action,":[149],"fate":[151],"after":[154],"receptor":[155],"binding":[156],"examined.":[158],"dIDE-transfected":[160],"displayed":[162],"increased":[163],"prebound":[166],"compared":[168],"This":[172],"observed":[177],"even":[178],"when":[179],"excess":[180],"unlabeled":[181],"added":[184],"block":[186],"reuptake":[187],"These":[191],"results":[192,236],"indicate":[193],"acts":[196],"at":[197],"least":[198],"part":[200],"within":[201],"cell.":[203],"lysosomotropic":[205],"agents":[206],"chloroquine":[207],"NH4Cl":[209],"did":[210],"affect":[212],"produced":[218],"transfection":[220],"lysosomal":[226],"IDE-mediated":[228],"pathways":[229],"are":[233],"independent.":[234],"demonstrate":[237],"intact":[247],"via":[249],"intracellular":[251],"pathway.":[252]},"counts_by_year":[{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":2},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":2},{"year":2012,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}