{"id":"https://openalex.org/W7166806159","doi":"https://doi.org/10.64898/2026.06.26.734712","title":"Accumulated Cytotoxicity Induced by Islet Amyloid Polypeptide Oligomers in Type 2 Diabetes","display_name":"Accumulated Cytotoxicity Induced by Islet Amyloid Polypeptide Oligomers in Type 2 Diabetes","publication_year":2026,"publication_date":"2026-07-01","ids":{"openalex":"https://openalex.org/W7166806159","doi":"https://doi.org/10.64898/2026.06.26.734712"},"language":"en","primary_location":{"id":"doi:10.64898/2026.06.26.734712","doi":"https://doi.org/10.64898/2026.06.26.734712","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.06.26.734712","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/07/01/2026.06.26.734712.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/07/01/2026.06.26.734712.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5075453637","display_name":"Andrey V. Kuznetsov","orcid":"https://orcid.org/0000-0002-2692-6907","observed_orcids":["https://orcid.org/0000-0002-2692-6907","https://orcid.org/0009-0002-8596-3086"]},"institutions":[{"id":"https://openalex.org/I137902535","display_name":"North Carolina State University","ror":"https://ror.org/04tj63d06","country_code":"US","type":"education","lineage":["https://openalex.org/I137902535"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Andrey V. Kuznetsov","raw_affiliation_strings":["Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA"],"raw_orcid":"https://orcid.org/0000-0002-2692-6907","affiliations":[{"raw_affiliation_string":"Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA","institution_ids":["https://openalex.org/I137902535"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5075453637"],"corresponding_institution_ids":["https://openalex.org/I137902535"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10839","display_name":"Pancreatic function and diabetes","score":0.8740000128746033,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"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/T10839","display_name":"Pancreatic function and diabetes","score":0.8740000128746033,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"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/T10086","display_name":"Alzheimer's disease research and treatments","score":0.09769999980926514,"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"}},{"id":"https://openalex.org/T10401","display_name":"Diabetes Treatment and Management","score":0.005200000014156103,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/amylin","display_name":"amylin","score":0.9909999966621399},{"id":"https://openalex.org/keywords/type-2-diabetes","display_name":"type 2 diabetes","score":0.9369999766349792},{"id":"https://openalex.org/keywords/beta-cell-dysfunction","display_name":"beta-cell dysfunction","score":0.8240000009536743},{"id":"https://openalex.org/keywords/oligomer-dissociation","display_name":"oligomer dissociation","score":0.7649999856948853},{"id":"https://openalex.org/keywords/amyloid-deposition","display_name":"amyloid deposition","score":0.7440000176429749},{"id":"https://openalex.org/keywords/beta-cell-secretion","display_name":"beta-cell secretion","score":0.6800000071525574},{"id":"https://openalex.org/keywords/sensitivity-analysis","display_name":"sensitivity analysis","score":0.7509999871253967},{"id":"https://openalex.org/keywords/therapeutic-target","display_name":"therapeutic target","score":0.8610000014305115}],"concepts":[{"id":"https://openalex.org/C165220095","wikidata":"https://www.wikidata.org/wiki/Q207524","display_name":"Islet","level":3,"score":0.8611999750137329},{"id":"https://openalex.org/C2780642029","wikidata":"https://www.wikidata.org/wiki/Q726004","display_name":"Oligomer","level":2,"score":0.8090999722480774},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7085000276565552},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.7067000269889832},{"id":"https://openalex.org/C2777633098","wikidata":"https://www.wikidata.org/wiki/Q2736051","display_name":"Amyloid (mycology)","level":2,"score":0.6789000034332275},{"id":"https://openalex.org/C27523624","wikidata":"https://www.wikidata.org/wiki/Q14860849","display_name":"Fibril","level":2,"score":0.6230999827384949},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.607200026512146},{"id":"https://openalex.org/C154317977","wikidata":"https://www.wikidata.org/wiki/Q376266","display_name":"Cytotoxic T cell","level":3,"score":0.5965999960899353},{"id":"https://openalex.org/C49039625","wikidata":"https://www.wikidata.org/wiki/Q84230","display_name":"Secretion","level":2,"score":0.46970000863075256},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.46939998865127563},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4690999984741211},{"id":"https://openalex.org/C166940927","wikidata":"https://www.wikidata.org/wiki/Q178827","display_name":"Monomer","level":3,"score":0.4496000111103058},{"id":"https://openalex.org/C148898269","wikidata":"https://www.wikidata.org/wiki/Q1108792","display_name":"Kinetics","level":2,"score":0.4081999957561493},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.36739999055862427},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.35109999775886536},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.34310001134872437},{"id":"https://openalex.org/C136238340","wikidata":"https://www.wikidata.org/wiki/Q7251455","display_name":"Protein aggregation","level":2,"score":0.3353999853134155},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.32170000672340393},{"id":"https://openalex.org/C2780705028","wikidata":"https://www.wikidata.org/wiki/Q424643","display_name":"Amylin","level":4,"score":0.3181000053882599},{"id":"https://openalex.org/C2909607560","wikidata":"https://www.wikidata.org/wiki/Q6740853","display_name":"Amyloid disease","level":5,"score":0.30250000953674316},{"id":"https://openalex.org/C2994168385","wikidata":"https://www.wikidata.org/wiki/Q6740853","display_name":"Amyloid fibril","level":4,"score":0.3005000054836273},{"id":"https://openalex.org/C2777180221","wikidata":"https://www.wikidata.org/wiki/Q3025883","display_name":"Type 2 diabetes","level":3,"score":0.29910001158714294},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.29840001463890076},{"id":"https://openalex.org/C2781449126","wikidata":"https://www.wikidata.org/wiki/Q288591","display_name":"Alpha-synuclein","level":4,"score":0.2558000087738037},{"id":"https://openalex.org/C2778886173","wikidata":"https://www.wikidata.org/wiki/Q53832","display_name":"Tetramer","level":3,"score":0.25040000677108765}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.06.26.734712","doi":"https://doi.org/10.64898/2026.06.26.734712","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.06.26.734712","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/07/01/2026.06.26.734712.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.06.26.734712","doi":"https://doi.org/10.64898/2026.06.26.734712","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.06.26.734712","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/07/01/2026.06.26.734712.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9537000060081482}],"study_designs":[],"awards":[{"id":"https://openalex.org/G4457031608","display_name":"DMS/NIGMS 1: Developing a mathematical framework to understand viral-cellular transduction for cellular reprogramming","funder_award_id":"2451660","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7166806159.pdf","grobid_xml":"https://content.openalex.org/works/W7166806159.grobid-xml"},"referenced_works_count":59,"referenced_works":["https://openalex.org/W1500760933","https://openalex.org/W1588092320","https://openalex.org/W1721240973","https://openalex.org/W1980744914","https://openalex.org/W1981793913","https://openalex.org/W1993327456","https://openalex.org/W2011923356","https://openalex.org/W2013579540","https://openalex.org/W2017622913","https://openalex.org/W2021388785","https://openalex.org/W2037487194","https://openalex.org/W2037588135","https://openalex.org/W2053670472","https://openalex.org/W2053684471","https://openalex.org/W2054243156","https://openalex.org/W2055775253","https://openalex.org/W2080225612","https://openalex.org/W2086427947","https://openalex.org/W2092305593","https://openalex.org/W2093226724","https://openalex.org/W2095481422","https://openalex.org/W2097259690","https://openalex.org/W2105955034","https://openalex.org/W2108781675","https://openalex.org/W2109728760","https://openalex.org/W2127632161","https://openalex.org/W2136989779","https://openalex.org/W2137204463","https://openalex.org/W2138041386","https://openalex.org/W2141035467","https://openalex.org/W2148869006","https://openalex.org/W2167218565","https://openalex.org/W2170552507","https://openalex.org/W2606611764","https://openalex.org/W2739631891","https://openalex.org/W2744679708","https://openalex.org/W2749647210","https://openalex.org/W2787708991","https://openalex.org/W2791242266","https://openalex.org/W2905961860","https://openalex.org/W2979307679","https://openalex.org/W2980377140","https://openalex.org/W2994736597","https://openalex.org/W3024506966","https://openalex.org/W3121120642","https://openalex.org/W3188295838","https://openalex.org/W3194560838","https://openalex.org/W4225004533","https://openalex.org/W4386118060","https://openalex.org/W4386594957","https://openalex.org/W4391262240","https://openalex.org/W4392297183","https://openalex.org/W4404765314","https://openalex.org/W4408229696","https://openalex.org/W4408378526","https://openalex.org/W4410696409","https://openalex.org/W4415756859","https://openalex.org/W7133301568","https://openalex.org/W7166517497"],"related_works":["https://openalex.org/W139940403","https://openalex.org/W2148869006","https://openalex.org/W2207649834","https://openalex.org/W2749647210","https://openalex.org/W1588092320","https://openalex.org/W2137204463","https://openalex.org/W2791242266","https://openalex.org/W1999909300","https://openalex.org/W130726298","https://openalex.org/W2155388842"],"abstract_inverted_index":{"Abstract":[0],"Type":[1],"2":[2,321],"diabetes":[3,322],"is":[4,68,117,142],"characterized":[5],"by":[6,263],"the":[7,16,36,40,44,72,78,81,89,103,108,112,121,125,153,161,185,207,249,253,260,270,284,299],"progressive":[8],"aggregation":[9,67],"of":[10,18,43,65,74,80,91,114,124,133,156,187,210,236,259,286,295],"islet":[11,261],"amyloid":[12,220,228,264],"polypeptide":[13],"(IAPP)":[14],"within":[15,96],"islets":[17],"Langerhans,":[19],"a":[20,62,97,129,147,169,231,242,325],"process":[21],"strongly":[22],"implicated":[23],"in":[24,275,319],"beta-cell":[25,75,291],"dysfunction":[26],"and":[27,47,54,77,88,93,128,160,181,193,219,293,307,323],"loss.":[28],"Although":[29],"oligomeric":[30],"IAPP":[31,66,157,297],"intermediates":[32],"are":[33,107],"widely":[34],"considered":[35],"principal":[37],"cytotoxic":[38,110,246,317],"species,":[39,111],"relative":[41],"contributions":[42],"numerous":[45],"biological":[46],"kinetic":[48],"processes":[49,288],"governing":[50],"their":[51],"formation,":[52],"clearance,":[53,85,204],"conversion":[55],"into":[56],"fibrils":[57],"remain":[58,191],"poorly":[59],"quantified.":[60],"Here,":[61],"mathematical":[63],"model":[64,140,199,254],"developed":[69],"that":[70,105,202,227],"incorporates":[71],"physiology":[73],"secretion":[76,159,251,306],"microanatomy":[79],"islet,":[82],"including":[83],"capillary-mediated":[84],"enzymatic":[86],"degradation,":[87],"kinetics":[90],"oligomer":[92,126,166,308],"fibril":[94,217],"formation":[95],"well-mixed":[98],"control":[99],"volume.":[100],"Building":[101],"on":[102,172],"hypothesis":[104],"oligomers":[106,211],"major":[109],"concept":[113],"accumulated":[115,174],"cytotoxicity":[116],"introduced,":[118],"defined":[119],"as":[120,290,310],"time":[122],"integral":[123],"concentration,":[127],"systematic":[130],"sensitivity":[131],"analysis":[132],"this":[134,280],"quantity":[135],"with":[136,176],"respect":[137],"to":[138,206],"all":[139,188],"parameters":[141,190],"conducted.":[143],"The":[144,198],"results":[145],"reveal":[146],"clear":[148],"hierarchy:":[149],"only":[150],"two":[151],"parameters,":[152],"basal":[154],"rate":[155,162],"monomer":[158,305],"constant":[163],"for":[164,245,315,328],"spontaneous":[165],"dissociation,":[167],"exert":[168],"first-order":[170],"influence":[171],"long-term":[173],"cytotoxicity,":[175,225],"dimensionless":[177],"sensitivities":[178],"approaching":[179],"+1":[180],"\u22121,":[182],"respectively,":[183],"while":[184],"effects":[186],"other":[189],"subordinate":[192],"diminish":[194],"at":[195],"long":[196],"times.":[197],"further":[200],"shows":[201],"capillary":[203],"owing":[205],"physical":[208],"exclusion":[209],"from":[212,298],"fenestrated":[213],"capillaries,":[214],"selectively":[215],"reduces":[216],"accumulation":[218],"deposition":[221],"without":[222],"affecting":[223],"oligomer-mediated":[224],"indicating":[226],"area":[229,262],"fraction,":[230],"commonly":[232],"used":[233],"histological":[234,278],"metric":[235],"disease":[237],"severity,":[238],"may":[239],"not":[240],"be":[241],"reliable":[243],"surrogate":[244],"burden.":[247],"At":[248],"highest":[250],"rate,":[252],"predicts":[255],"approximately":[256],"48%":[257],"replacement":[258],"after":[265],"30":[266],"years,":[267],"substantially":[268],"below":[269],"more":[271],"than":[272],"85%":[273],"reported":[274],"some":[276],"end-stage":[277],"studies;":[279],"gap":[281],"likely":[282],"reflects":[283],"omission":[285],"late-stage":[287],"such":[289],"death":[292],"release":[294],"intracellular":[296],"present":[300],"model.":[301],"These":[302],"findings":[303],"identify":[304],"dissociation":[309],"potentially":[311],"promising":[312],"therapeutic":[313],"targets":[314],"limiting":[316],"damage":[318],"type":[320],"provide":[324],"quantitative":[326],"framework":[327],"evaluating":[329],"candidate":[330],"intervention":[331],"strategies.":[332]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-07-02T00:00:00"}
