{"id":"https://openalex.org/W2104623692","doi":"https://doi.org/10.2337/diabetes.53.7.1824","title":"Direct Insulin Signaling of Neurons Reverses Diabetic Neuropathy","display_name":"Direct Insulin Signaling of Neurons Reverses Diabetic Neuropathy","publication_year":2004,"publication_date":"2004-07-01","ids":{"openalex":"https://openalex.org/W2104623692","doi":"https://doi.org/10.2337/diabetes.53.7.1824","mag":"2104623692","pmid":"https://pubmed.ncbi.nlm.nih.gov/15220207"},"language":"en","primary_location":{"id":"doi:10.2337/diabetes.53.7.1824","doi":"https://doi.org/10.2337/diabetes.53.7.1824","is_oa":false,"landing_page_url":"https://doi.org/10.2337/diabetes.53.7.1824","pdf_url":null,"source":{"id":"https://openalex.org/S129060628","display_name":"Diabetes","issn_l":"0012-1797","issn":["0012-1797","1939-327X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320274","host_organization_name":"American Diabetes Association","host_organization_lineage":["https://openalex.org/P4310320274"],"host_organization_lineage_names":["American Diabetes Association"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Diabetes","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5077812351","display_name":"Valentine Brussee","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I168635309","display_name":"University of Calgary","ror":"https://ror.org/03yjb2x39","country_code":"CA","type":"education","lineage":["https://openalex.org/I168635309"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Valentine Brussee","raw_affiliation_strings":["From the Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada","institution_ids":["https://openalex.org/I168635309"]}]},{"author_position":"middle","author":{"id":null,"display_name":"F. Alexander Cunningham","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I168635309","display_name":"University of Calgary","ror":"https://ror.org/03yjb2x39","country_code":"CA","type":"education","lineage":["https://openalex.org/I168635309"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"F. Alexander Cunningham","raw_affiliation_strings":["From the Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada","institution_ids":["https://openalex.org/I168635309"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5035802220","display_name":"Douglas William Zochodne","orcid":"https://orcid.org/0000-0003-1692-5983","observed_orcids":["https://orcid.org/0000-0003-1692-5983"]},"institutions":[{"id":"https://openalex.org/I168635309","display_name":"University of Calgary","ror":"https://ror.org/03yjb2x39","country_code":"CA","type":"education","lineage":["https://openalex.org/I168635309"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Douglas W. Zochodne","raw_affiliation_strings":["From the Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"From the Department of Clinical Neurosciences and the Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada","institution_ids":["https://openalex.org/I168635309"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I168635309"],"apc_list":null,"apc_paid":null,"fwci":7.4048,"has_fulltext":false,"cited_by_count":230,"citation_normalized_percentile":{"value":0.98000145,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":97,"max":100},"biblio":{"volume":"53","issue":"7","first_page":"1824","last_page":"1830"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10196","display_name":"Pain Mechanisms and Treatments","score":0.5967000126838684,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10196","display_name":"Pain Mechanisms and Treatments","score":0.5967000126838684,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"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/T11735","display_name":"Peripheral Neuropathies and Disorders","score":0.34769999980926514,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"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/T10483","display_name":"Nerve injury and regeneration","score":0.012799999676644802,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/diabetic-polyneuropathy","display_name":"diabetic polyneuropathy","score":0.9079999923706055},{"id":"https://openalex.org/keywords/insulin-signaling","display_name":"insulin signaling","score":0.7910000085830688},{"id":"https://openalex.org/keywords/insulin-receptor","display_name":"insulin receptor","score":0.7749999761581421},{"id":"https://openalex.org/keywords/sensory-neurons","display_name":"sensory neurons","score":0.8690000176429749},{"id":"https://openalex.org/keywords/dorsal-root-ganglia","display_name":"dorsal root ganglia","score":0.7139999866485596},{"id":"https://openalex.org/keywords/axonal-atrophy","display_name":"axonal atrophy","score":0.7770000100135803},{"id":"https://openalex.org/keywords/conduction-velocity","display_name":"conduction velocity","score":0.7979999780654907},{"id":"https://openalex.org/keywords/insulin-like-growth-factor-i","display_name":"insulin-like growth factor I","score":0.718999981880188},{"id":"https://openalex.org/keywords/streptozotocin-induced-diabetes","display_name":"streptozotocin-induced diabetes","score":0.9089999794960022},{"id":"https://openalex.org/keywords/insulin-antibodies","display_name":"insulin antibodies","score":0.8769999742507935},{"id":"https://openalex.org/keywords/cerebrospinal-fluid","display_name":"cerebrospinal fluid","score":0.8740000128746033},{"id":"https://openalex.org/keywords/peripheral-neuropathy","display_name":"peripheral neuropathy","score":0.48899999260902405}],"concepts":[{"id":"https://openalex.org/C2779306644","wikidata":"https://www.wikidata.org/wiki/Q2002370","display_name":"Insulin","level":2,"score":0.8034434914588928},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6576247215270996},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.6519975662231445},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.6482623815536499},{"id":"https://openalex.org/C112446052","wikidata":"https://www.wikidata.org/wiki/Q422579","display_name":"Insulin receptor","level":4,"score":0.634698748588562},{"id":"https://openalex.org/C555293320","wikidata":"https://www.wikidata.org/wiki/Q12206","display_name":"Diabetes mellitus","level":2,"score":0.6068605184555054},{"id":"https://openalex.org/C2776281502","wikidata":"https://www.wikidata.org/wiki/Q1395415","display_name":"Dorsal root ganglion","level":3,"score":0.5913059115409851},{"id":"https://openalex.org/C2779280383","wikidata":"https://www.wikidata.org/wiki/Q257331","display_name":"Streptozotocin","level":3,"score":0.4766046404838562},{"id":"https://openalex.org/C2779901536","wikidata":"https://www.wikidata.org/wiki/Q945238","display_name":"Peripheral neuropathy","level":3,"score":0.46823614835739136},{"id":"https://openalex.org/C2775908076","wikidata":"https://www.wikidata.org/wiki/Q3142126","display_name":"Sensory neuron","level":3,"score":0.44073486328125},{"id":"https://openalex.org/C2780775167","wikidata":"https://www.wikidata.org/wiki/Q9606","display_name":"Spinal cord","level":2,"score":0.2713125944137573},{"id":"https://openalex.org/C529278444","wikidata":"https://www.wikidata.org/wiki/Q47273","display_name":"Central nervous system","level":2,"score":0.2466963529586792},{"id":"https://openalex.org/C2777391703","wikidata":"https://www.wikidata.org/wiki/Q1053470","display_name":"Insulin resistance","level":3,"score":0.2355269491672516},{"id":"https://openalex.org/C118552586","wikidata":"https://www.wikidata.org/wiki/Q7867","display_name":"Psychiatry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000906","descriptor_name":"Antibodies","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D001284","descriptor_name":"Atrophy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001369","descriptor_name":"Axons","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D001369","descriptor_name":"Axons","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D003921","descriptor_name":"Diabetes Mellitus, Experimental","qualifier_ui":"Q000150","qualifier_name":"complications","is_major_topic":false},{"descriptor_ui":"D003921","descriptor_name":"Diabetes Mellitus, Experimental","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D003929","descriptor_name":"Diabetic Neuropathies","qualifier_ui":"Q000209","qualifier_name":"etiology","is_major_topic":false},{"descriptor_ui":"D003929","descriptor_name":"Diabetic Neuropathies","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D003929","descriptor_name":"Diabetic Neuropathies","qualifier_ui":"Q000503","qualifier_name":"physiopathology","is_major_topic":true},{"descriptor_ui":"D007278","descriptor_name":"Injections, Spinal","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007279","descriptor_name":"Injections, Subcutaneous","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007328","descriptor_name":"Insulin","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D007328","descriptor_name":"Insulin","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":false},{"descriptor_ui":"D007328","descriptor_name":"Insulin","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D007334","descriptor_name":"Insulin-Like Growth Factor I","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":false},{"descriptor_ui":"D009474","descriptor_name":"Neurons","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D009475","descriptor_name":"Neurons, Afferent","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D017207","descriptor_name":"Rats, Sprague-Dawley","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.2337/diabetes.53.7.1824","doi":"https://doi.org/10.2337/diabetes.53.7.1824","is_oa":false,"landing_page_url":"https://doi.org/10.2337/diabetes.53.7.1824","pdf_url":null,"source":{"id":"https://openalex.org/S129060628","display_name":"Diabetes","issn_l":"0012-1797","issn":["0012-1797","1939-327X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320274","host_organization_name":"American Diabetes Association","host_organization_lineage":["https://openalex.org/P4310320274"],"host_organization_lineage_names":["American Diabetes Association"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Diabetes","raw_type":"journal-article"},{"id":"pmid:15220207","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15220207","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":"Diabetes","raw_type":"Journal Article"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.828.233","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.828.233","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"http://diabetes.diabetesjournals.org/content/53/7/1824.full.pdf","raw_type":"text"},{"id":"mag:2188560107","doi":null,"is_oa":false,"landing_page_url":"http://diabetes.diabetesjournals.org/content/53/7/1824.full.pdf","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320309829","display_name":"Canadian Diabetes Association","ror":"https://ror.org/00arvcr78"},{"id":"https://openalex.org/F4320334506","display_name":"Canadian Institutes of Health Research","ror":"https://ror.org/01gavpb45"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":44,"referenced_works":["https://openalex.org/W3712366","https://openalex.org/W106142053","https://openalex.org/W566970497","https://openalex.org/W1590376803","https://openalex.org/W1609815362","https://openalex.org/W1903272649","https://openalex.org/W1965634002","https://openalex.org/W1968301153","https://openalex.org/W1973584991","https://openalex.org/W1980735721","https://openalex.org/W1986184217","https://openalex.org/W1992699922","https://openalex.org/W1996424575","https://openalex.org/W1997449321","https://openalex.org/W1998028800","https://openalex.org/W2005155920","https://openalex.org/W2005485195","https://openalex.org/W2017826101","https://openalex.org/W2021968018","https://openalex.org/W2030550361","https://openalex.org/W2033552617","https://openalex.org/W2040790649","https://openalex.org/W2046998604","https://openalex.org/W2067033230","https://openalex.org/W2069527051","https://openalex.org/W2078920527","https://openalex.org/W2083264147","https://openalex.org/W2087868042","https://openalex.org/W2104386629","https://openalex.org/W2110554814","https://openalex.org/W2113716304","https://openalex.org/W2115177689","https://openalex.org/W2115836749","https://openalex.org/W2126054531","https://openalex.org/W2141277427","https://openalex.org/W2148978926","https://openalex.org/W2155217360","https://openalex.org/W2155351425","https://openalex.org/W2159147867","https://openalex.org/W2163420794","https://openalex.org/W2166483018","https://openalex.org/W2221181442","https://openalex.org/W2315007199","https://openalex.org/W2769264260"],"related_works":["https://openalex.org/W2188560107","https://openalex.org/W7098381955","https://openalex.org/W4327701137","https://openalex.org/W2562461810","https://openalex.org/W1998028800","https://openalex.org/W2056933324","https://openalex.org/W832234686","https://openalex.org/W2067198165","https://openalex.org/W1945886162","https://openalex.org/W2070302167"],"abstract_inverted_index":{"Diabetic":[0],"polyneuropathy":[1],"is":[2,15,43],"the":[3,10,57,120,127,159,187,215,221],"most":[4],"common":[5],"acquired":[6],"diffuse":[7],"disorder":[8],"of":[9,37,59,70,73,96,129,206,223],"peripheral":[11,53,209,225],"nervous":[12],"system.":[13],"It":[14],"generally":[16],"assumed":[17],"that":[18,46,65,137,155,213],"insulin":[19,50,74,109,125,140,160,173,207],"benefits":[20],"human":[21],"and":[22,39,41,93,98,110,144,183],"experimental":[23],"diabetic":[24,105,224],"neuropathy":[25],"indirectly":[26],"by":[27,135,165,193,197],"lowering":[28],"glucose":[29],"levels.":[30],"Insulin":[31],"also":[32],"provides":[33],"potent":[34],"direct":[35,49,66,204],"support":[36],"neurons":[38,54,132,157,210],"axons,":[40],"there":[42],"a":[44],"possibility":[45],"abnormalities":[47],"in":[48,102,115,119,174,189],"signaling":[51,130,205],"on":[52,208],"relate":[55,219],"to":[56,79,220],"development":[58,222],"this":[60],"disorder.":[61],"Here":[62],"we":[63,153,170],"report":[64],"neuronal":[67],"(intrathecal)":[68],"delivery":[69],"low":[71],"doses":[72],"(0.1-0.2":[75],"IU":[76],"daily),":[77],"insufficient":[78],"reduce":[80],"glycemia":[81],"or":[82,89],"equimolar":[83],"IGF-I":[84,111],"but":[85,195],"not":[86,196],"intrathecal":[87,124,172],"saline":[88],"subcutaneous":[90],"insulin,":[91],"improved":[92],"reversed":[94,113],"slowing":[95,182],"motor":[97],"sensory":[99,117,131],"conduction":[100],"velocity":[101],"rats":[103,176],"rendered":[104],"using":[106,177],"streptozotocin.":[107],"Moreover,":[108,152],"similarly":[112],"atrophy":[114,185],"myelinated":[116],"axons":[118],"sural":[121],"nerve.":[122],"That":[123],"had":[126],"capability":[128],"was":[133],"confirmed":[134,154],"observing":[136],"fluorescein":[138],"isothiocyanate-labeled":[139],"given":[141],"intrathecally":[142],"accessed":[143],"labeled":[145],"individual":[146],"lumbar":[147],"dorsal":[148],"root":[149],"ganglion":[150],"neurons.":[151],"such":[156],"express":[158],"receptor,":[161],"as":[162],"previously":[163],"suggested":[164],"Sugimoto":[166],"et":[167],"al.":[168],"Finally,":[169],"sequestered":[171],"nondiabetic":[175],"an":[178,198],"anti-insulin":[179,194],"antibody.":[180],"Conduction":[181],"axonal":[184],"resembling":[186],"changes":[188],"diabetes":[190],"were":[191],"generated":[192],"anti-rat":[199],"albumin":[200],"antibody":[201],"infusion.":[202],"Defective":[203],"through":[211],"routes":[212],"include":[214],"cerebrospinal":[216],"fluid":[217],"may":[218],"neuropathy.":[226]},"counts_by_year":[{"year":2026,"cited_by_count":11},{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":5},{"year":2023,"cited_by_count":11},{"year":2022,"cited_by_count":12},{"year":2021,"cited_by_count":8},{"year":2020,"cited_by_count":11},{"year":2019,"cited_by_count":7},{"year":2018,"cited_by_count":11},{"year":2017,"cited_by_count":9},{"year":2016,"cited_by_count":8},{"year":2015,"cited_by_count":15},{"year":2014,"cited_by_count":21},{"year":2013,"cited_by_count":14},{"year":2012,"cited_by_count":10}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}
