{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T21:10:21Z","timestamp":1771103421823,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"national funds","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"national funds","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"national funds","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"national funds","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"national funds","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"national funds","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"national funds","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"national funds","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"national funds","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"Institute for Research and Innovation in Health Sciences","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"Norte Portugal Regional Operational Programme","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]},{"name":"European Regional Development Fund (ERDF)","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"European Regional Development Fund (ERDF)","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"European Regional Development Fund (ERDF)","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"European Regional Development Fund (ERDF)","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"European Regional Development Fund (ERDF)","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"European Regional Development Fund (ERDF)","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"European Regional Development Fund (ERDF)","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"European Regional Development Fund (ERDF)","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"European Regional Development Fund (ERDF)","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"The Porto Comprehensive Cancer Center","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]},{"name":"FCT Ph.D. grant","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"FCT Ph.D. grant","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"FCT Ph.D. grant","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"FCT Ph.D. grant","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"FCT Ph.D. grant","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"FCT Ph.D. grant","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"FCT Ph.D. grant","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"FCT Ph.D. grant","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"FCT Ph.D. grant","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior-Brazil (CAPES)","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"CNE-FAPERJ E-26\/200.798\/2021","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["SFRH\/BD\/129431\/2017"],"award-info":[{"award-number":["SFRH\/BD\/129431\/2017"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["CEECIND\/00201\/2017"],"award-info":[{"award-number":["CEECIND\/00201\/2017"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["2022.00276.CEECIND"],"award-info":[{"award-number":["2022.00276.CEECIND"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["UID\/BIM\/04293\/2019"],"award-info":[{"award-number":["UID\/BIM\/04293\/2019"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["NORTE 2020"],"award-info":[{"award-number":["NORTE 2020"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678-Cons\u00f3rcio PORTO.CCC\u2013Porto.Comprehensive"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["SFRH\/BD\/137802\/2018"],"award-info":[{"award-number":["SFRH\/BD\/137802\/2018"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["88881.361674\/2019-01"],"award-info":[{"award-number":["88881.361674\/2019-01"]}]},{"name":"Programa de Redes de Pesquisa em Sa\u00fade do Estado do Rio de Janeiro","award":["2019 E-26\/010.002429\/2019"],"award-info":[{"award-number":["2019 E-26\/010.002429\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Atrx loss was recently ascertained as insufficient to drive pancreatic neuroendocrine tumour (PanNET) formation in mice islets. We have identified a preponderant role of Atrx in the endocrine dysfunction in a Rip-Cre;AtrxKO genetically engineered mouse model (GEMM). To validate the impact of a different Cre-driver line, we used similar methodologies and characterised the Pdx1-Cre;AtrxKO (P.AtrxKO) GEMM to search for PanNET formation and endocrine fitness disruption for a period of up to 24 months. Male and female mice presented different phenotypes. Compared to P.AtrxWT, P.AtrxHOM males were heavier during the entire study period, hyperglycaemic between 3 and 12 mo., and glucose intolerant only from 6 mo.; in contrast, P.AtrxHOM females started exhibiting increased weight gains later (after 6 mo.), but diabetes or glucose intolerance was detected by 3 mo. Overall, all studied mice were overweight or obese from early ages, which challenged the histopathological evaluation of the pancreas and liver, especially after 12 mo. Noteworthily, losing Atrx predisposed mice to an increase in intrapancreatic fatty infiltration (FI), peripancreatic fat deposition, and macrovesicular steatosis. As expected, no animal developed PanNETs. An obese diabetic GEMM of disrupted Atrx is presented as potentially useful for metabolic studies and as a putative candidate for inserting additional tumourigenic genetic events.<\/jats:p>","DOI":"10.3390\/cancers15113018","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T01:33:54Z","timestamp":1685669634000},"page":"3018","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Generation of an Obese Diabetic Mouse Model upon Conditional Atrx Disruption"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-7869","authenticated-orcid":false,"given":"Tiago Bordeira","family":"Gaspar","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"given":"Tito Teles","family":"Jesus","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"given":"Maria Teresa","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7752-998X","authenticated-orcid":false,"given":"Sofia","family":"Macedo","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"given":"Mariana Alves","family":"Soares","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Laborat\u00f3rio de Endocrinologia Experimental (LEEx), Instituto de Ci\u00eancias Biom\u00e9dicas (ICB), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1349-3281","authenticated-orcid":false,"given":"Rui Sousa","family":"Martins","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Faculty of Sciences of the University of Porto (FCUP), 4169-007 Porto, Portugal"}]},{"given":"R\u00faben","family":"Leite","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"School of Health (ESS), Polytechnic Institute of Porto (IPP), Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Lia","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3517-2462","authenticated-orcid":false,"given":"Daniela Ferreira","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular and Cell Biology (IBMC), University of Porto, 4200-135 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}]},{"given":"In\u00eas","family":"Borges","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico Veterin\u00e1rio (Cedivet), 4200-071 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-1323","authenticated-orcid":false,"given":"Sule","family":"Canberk","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-0086","authenticated-orcid":false,"given":"F\u00e1tima","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7832-8717","authenticated-orcid":false,"given":"Leandro","family":"Miranda-Alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Endocrinologia Experimental (LEEx), Instituto de Ci\u00eancias Biom\u00e9dicas (ICB), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8597-3474","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"Lopes","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o (CHUSJ), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9607-6998","authenticated-orcid":false,"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0871-1427","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Vinagre","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1093\/hmg\/3.11.1957","article-title":"Cloning and characterization of a new human Xq13 gene, encoding a putative helicase","volume":"3","author":"Stayton","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1093\/hmg\/5.12.1899","article-title":"ATRX encodes a novel member of the SNF2 family of proteins: Mutations point to a common mechanism underlying the ATR-X syndrome","volume":"5","author":"Picketts","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/hmg\/3.1.39","article-title":"Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3","volume":"3","author":"Gecz","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1080\/14728222.2018.1487953","article-title":"Mutant ATRX: Uncovering a new therapeutic target for glioma","volume":"22","author":"Haase","year":"2018","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Valenzuela, M., Amato, R., Sgura, A., Antoccia, A., and Berardinelli, F. (2021). The Multiple Facets of ATRX Protein. Cancers, 13.","DOI":"10.3390\/cancers13092211"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/humu.20734","article-title":"Mutations in the chromatin-associated protein ATRX","volume":"29","author":"Gibbons","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nsmb.2062","article-title":"ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome","volume":"18","author":"Iwase","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1093\/hmg\/ddr107","article-title":"The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9","volume":"20","author":"Dhayalan","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20369","DOI":"10.1074\/jbc.M401321200","article-title":"A novel transcription regulatory complex containing death domain-associated protein and the ATR-X syndrome protein","volume":"279","author":"Tang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1038\/s41467-017-01206-y","article-title":"Structural and mechanistic insights into ATRX-dependent and -independent functions of the histone chaperone DAXX","volume":"8","author":"Hoelper","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a026567","DOI":"10.1101\/cshperspect.a026567","article-title":"ATRX and DAXX: Mechanisms and Mutations","volume":"7","author":"Dyer","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.cell.2010.01.003","article-title":"Distinct factors control histone variant H3.3 localization at specific genomic regions","volume":"140","author":"Goldberg","year":"2010","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10635","DOI":"10.1073\/pnas.1937626100","article-title":"The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies","volume":"100","author":"Xue","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Amorim, J.P., Santos, G., Vinagre, J., and Soares, P. (2016). The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype. Genes, 7.","DOI":"10.3390\/genes7090066"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7538","DOI":"10.1038\/ncomms8538","article-title":"Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX","volume":"6","author":"Clynes","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sanchez-Martin, V., Soriano, M., and Garcia-Salcedo, J.A. (2021). Quadruplex Ligands in Cancer Therapy. Cancers, 13.","DOI":"10.3390\/cancers13133156"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nature14345","article-title":"Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells","volume":"522","author":"Elsasser","year":"2015","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eaba8415","DOI":"10.1126\/sciadv.aba8415","article-title":"Daxx maintains endogenous retroviral silencing and restricts cellular plasticity in vivo","volume":"6","author":"Wasylishen","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tsai, K., Thikmyanova, N., Wojcechowskyj, J.A., Delecluse, H.J., and Lieberman, P.M. (2011). EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002376"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1128\/JVI.02308-07","article-title":"Replication of ICP0-null mutant herpes simplex virus type 1 is restricted by both PML and Sp100","volume":"82","author":"Everett","year":"2008","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1128\/JVI.02950-12","article-title":"Components of promyelocytic leukemia nuclear bodies (ND10) act cooperatively to repress herpesvirus infection","volume":"87","author":"Glass","year":"2013","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1126\/science.1200609","article-title":"DAXX\/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors","volume":"331","author":"Jiao","year":"2011","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1038\/ncomms3810","article-title":"Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1","volume":"4","author":"Cao","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nature21063","article-title":"Whole-genome landscape of pancreatic neuroendocrine tumours","volume":"543","author":"Scarpa","year":"2017","journal-title":"Nature"},{"key":"ref_25","unstructured":"cBioPortal for Cancer Genomics (2022, January 01). Gene Query, 118 Samples, 2 Genes. Available online: https:\/\/bit.ly\/3eKEkoi."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lovejoy, C.A., Li, W., Reisenweber, S., Thongthip, S., Bruno, J., de Lange, T., De, S., Petrini, J.H., Sung, P.A., and Jasin, M. (2012). Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002772"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1053\/j.gastro.2013.10.020","article-title":"Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors","volume":"146","author":"Marinoni","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1158\/1078-0432.CCR-16-1113","article-title":"Alternative Lengthening of Telomeres and Loss of DAXX\/ATRX Expression Predicts Metastatic Disease and Poor Survival in Patients with Pancreatic Neuroendocrine Tumors","volume":"23","author":"Singhi","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1158\/1078-0432.CCR-16-1147","article-title":"Alternative Lengthening of Telomeres in Primary Pancreatic Neuroendocrine Tumors Is Associated with Aggressive Clinical Behavior and Poor Survival","volume":"23","author":"Kim","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gaspar, T.B., Sa, A., Lopes, J.M., Sobrinho-Simoes, M., Soares, P., and Vinagre, J. (2018). Telomere Maintenance Mechanisms in Cancer. Genes, 9.","DOI":"10.3390\/genes9050241"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.humpath.2018.07.032","article-title":"ATRX loss is an independent predictor of poor survival in pancreatic neuroendocrine tumors","volume":"82","author":"Chou","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1053\/j.gastro.2018.02.026","article-title":"Loss of Chromatin-Remodeling Proteins and\/or CDKN2A Associates with Metastasis of Pancreatic Neuroendocrine Tumors and Reduced Patient Survival Times","volume":"154","author":"Roy","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R191","DOI":"10.1530\/ERC-22-0166","article-title":"An update on genetically engineered mouse models of pancreatic neuroendocrine neoplasms","volume":"29","author":"Gaspar","year":"2022","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gaspar, T.B., Macedo, S., Sa, A., Soares, M.A., Rodrigues, D.F., Sousa, M., Mendes, N., Martins, R.S., Cardoso, L., and Borges, I. (2022). Characterisation of an Atrx Conditional Knockout Mouse Model: Atrx Loss Causes Endocrine Dysfunction Rather Than Pancreatic Neuroendocrine Tumour. Cancers, 14.","DOI":"10.3390\/cancers14163865"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"dmm049552","DOI":"10.1242\/dmm.049552","article-title":"Context matters\u2014Daxx and Atrx are not robust tumor suppressors in the murine endocrine pancreas","volume":"15","author":"Sun","year":"2022","journal-title":"Dis. Model. Mech."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jcmgh.2018.09.004","article-title":"The Loss of ATRX Increases Susceptibility to Pancreatic Injury and Oncogenic KRAS in Female but Not Male Mice","volume":"7","author":"Young","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_37","unstructured":"The Jackson Laboratory (2022, November 01). B6.Cg-Tg(Ins2-cre)25Mgn\/J. Stock No: 003573. RIP-Cre. Available online: https:\/\/www.jax.org\/strain\/003573."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/s41591-019-0493-4","article-title":"Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors","volume":"25","author":"Cejas","year":"2019","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s42003-020-01479-y","article-title":"Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression","volume":"3","author":"Pipinikas","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1172\/JCI200522329","article-title":"The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis","volume":"115","author":"Mangelsdorf","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Garrick, D., Sharpe, J.A., Arkell, R., Dobbie, L., Smith, A.J., Wood, W.G., Higgs, D.R., and Gibbons, R.J. (2006). Loss of Atrx affects trophoblast development and the pattern of X-inactivation in extraembryonic tissues. PLoS Genet., 2.","DOI":"10.1371\/journal.pgen.0020058"},{"key":"ref_42","unstructured":"Mouse Genome Informatics (2022, January 01). Atrxtm1Rjg. Available online: http:\/\/www.informatics.jax.org\/allele\/MGI:3528480."},{"key":"ref_43","unstructured":"Mouse Genome Informatics (2023, February 15). B6.FVB-Tg(Pdx1-cre)6Tuv\/J. Available online: https:\/\/www.informatics.jax.org\/strain\/MGI:5293639."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"du Sert, N.P., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., Dirnagl, U., and Emerson, M. (2020). Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000411"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1293\/tox.2016-0016","article-title":"A comparison of the anatomical structure of the pancreas in experimental animals","volume":"29","author":"Tsuchitani","year":"2016","journal-title":"J. Toxicol. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Liang, W., Menke, A.L., Driessen, A., Koek, G.H., Lindeman, J.H., Stoop, R., Havekes, L.M., Kleemann, R., and van den Hoek, A.M. (2014). Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115922"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"154704","DOI":"10.1016\/j.metabol.2021.154704","article-title":"Maternal high-fat high-sucrose diet and gestational exercise modulate hepatic fat accumulation and liver mitochondrial respiratory capacity in mothers and male offspring","volume":"116","author":"Beleza","year":"2021","journal-title":"Metabolism"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"439","DOI":"10.2147\/DMSO.S234665","article-title":"Guidelines and Considerations for Metabolic Tolerance Tests in Mice","volume":"13","author":"Ramadori","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1213\/ANE.0000000000002864","article-title":"Correlation Coefficients: Appropriate Use and Interpretation","volume":"126","author":"Schober","year":"2018","journal-title":"Anesth. Analg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1530\/ERC-16-0554","article-title":"Hypo-methylation mediates chromosomal instability in pancreatic NET","volume":"24","author":"Marinoni","year":"2017","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s13148-011-0032-8","article-title":"Long interspersed nuclear element-1 hypomethylation in cancer: Biology and clinical applications","volume":"2","author":"Kitkumthorn","year":"2011","journal-title":"Clin. Epigenetics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"R315","DOI":"10.1530\/ERC-17-0012","article-title":"Genetic and epigenetic drivers of neuroendocrine tumours (NET)","volume":"24","author":"Wiedmer","year":"2017","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s11912-021-01096-w","article-title":"Alternative Lengthening of Telomeres (ALT) in Pancreatic Neuroendocrine Tumors: Ready for Prime-Time in Clinical Practice?","volume":"23","author":"Luchini","year":"2021","journal-title":"Curr. Oncol. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1136\/gutjnl-2021-324664","article-title":"Prognostic value of DAXX\/ATRX loss of expression and ALT activation in PanNETs: Is it time for clinical implementation?","volume":"71","author":"Marinoni","year":"2022","journal-title":"Gut"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1111\/cas.13766","article-title":"Fatty pancreas: A possible risk factor for pancreatic cancer in animals and humans","volume":"109","author":"Takahashi","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<139::AID-GENE12>3.0.CO;2-7","article-title":"Analysis of the Cre-mediated recombination driven by rat insulin promoter in embryonic and adult mouse pancreas","volume":"26","author":"Gannon","year":"2000","journal-title":"Genesis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cmet.2013.06.011","article-title":"Pancreas-specific Cre driver lines and considerations for their prudent use","volume":"18","author":"Magnuson","year":"2013","journal-title":"Cell Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1074\/jbc.M512373200","article-title":"RIP-Cre revisited, evidence for impairments of pancreatic beta-cell function","volume":"281","author":"Lee","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1055\/s-2007-976538","article-title":"Alterations of pancreatic beta-cell mass and islet number due to Ins2-controlled expression of Cre recombinase: RIP-Cre revisited; part 2","volume":"39","author":"Pomplun","year":"2007","journal-title":"Horm. Metab. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.redox.2017.12.015","article-title":"Age-related oxidative changes in pancreatic islets are predominantly located in the vascular system","volume":"15","author":"Kehm","year":"2018","journal-title":"Redox Biol."},{"key":"ref_62","unstructured":"Treutin, P.M., Dintzis, S.M., and Montine, K.S. (2018). Comparative Anatomy and Histology. A Mouse, Rat, and Human Atlas, 2 ed., Elsevier."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1159\/000507457","article-title":"Pancreatic Fat Infiltration Is Associated with a Higher Risk of Pancreatic Ductal Adenocarcinoma","volume":"36","author":"Desai","year":"2020","journal-title":"Visc. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.bbalip.2009.09.018","article-title":"Drug-induced lipotoxicity: Lipodystrophy associated with HIV-1 infection and antiretroviral treatment","volume":"1801","author":"Villarroya","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1038\/ajg.2009.466","article-title":"Risk factors for sporadic pancreatic endocrine tumors: A case-control study of prospectively evaluated patients","volume":"104","author":"Capurso","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"36073","DOI":"10.1038\/srep36073","article-title":"Risk Factors for Sporadic Pancreatic Neuroendocrine Tumors: A Case-Control Study","volume":"6","author":"Ben","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"615082","DOI":"10.3389\/fendo.2020.615082","article-title":"Diabetes in Patients with Pancreatic Neuroendocrine Neoplasms","volume":"11","author":"Zhuge","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.amjsurg.2022.05.026","article-title":"Prognostic value of preoperative diabetes mellitus in patients with non-functional pancreatic neuroendocrine neoplasms","volume":"224","author":"Tan","year":"2022","journal-title":"Am. J. Surg."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Santos, A.P., Santos, A.C., Castro, C., Raposo, L., Pereira, S.S., Torres, I., Henrique, R., Cardoso, H., and Monteiro, M.P. (2018). Visceral Obesity and Metabolic Syndrome Are Associated with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors. Cancers, 10.","DOI":"10.3390\/cancers10090293"},{"key":"ref_70","unstructured":"(2022, September 04). Diabetesatlas.org. IDF Diabetes Atlas. Available online: https:\/\/diabetesatlas.org\/."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"18614","DOI":"10.1038\/s41598-019-55156-0","article-title":"DAXX mutations as potential genomic markers of malignant evolution in small nonfunctioning pancreatic neuroendocrine tumors","volume":"9","author":"Cives","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1136\/gutjnl-2018-317233","article-title":"Whole-genome sequencing reveals distinct genetic bases for insulinomas and non-functional pancreatic neuroendocrine tumours: Leading to a new classification system","volume":"69","author":"Hong","year":"2020","journal-title":"Gut"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/11\/3018\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:46:56Z","timestamp":1760125616000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/11\/3018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,1]]},"references-count":72,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["cancers15113018"],"URL":"https:\/\/doi.org\/10.3390\/cancers15113018","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,1]]}}}