{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:16:36Z","timestamp":1784556996370,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The simultaneous characterization of histological alterations and distinct cell death pathways associated with diabetic cardiomyopathy (DCM) has not been comprehensively explored and may differ depending on the experimental model. We evaluated cardiac histological changes and markers of apoptosis, cell death associated with mitochondrial permeability transition pore (mPTP) opening (necrosis), and autophagy in early and advanced stages of streptozotocin (STZ)\u2010induced diabetes in rats receiving insulin daily to prevent mortality while maintaining hyperglycemia. Adult male Sprague\u2013Dawley rats (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094\u20135) were randomly assigned to receive STZ (diabetic group) or saline (mock) and followed up for 4 or 12\u2009weeks. Hearts were processed for histological examination and immunohistochemical detection of active caspase\u20103, beclin\u20101, and cyclophilin D. STZ significantly increased glycemia at both time points, whereas body weight reduction was observed only at 12\u2009weeks. No evidence of cardiac hypertrophy, fibrosis, or structural injury was detected in diabetic rats at either stage. Expression of caspase\u20103, beclin\u20101, and cyclophilin D decreased at 12\u2009weeks compared with 4\u2009weeks, regardless of treatment; however, cyclophilin D was elevated in diabetic hearts at 4\u2009weeks. These results suggest an early susceptibility to mPTP opening under persistent hyperglycemia, despite the absence of overt histological damage. They also underscore the critical importance of insulin dosing and study duration when interpreting data from STZ\u2010based models. Further studies are warranted to determine how even minimal insulin administration may shape the temporal dynamics of cell death during the progression of DCM.\n                  <\/jats:p>","DOI":"10.1002\/ame2.70225","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:10:54Z","timestamp":1778818254000},"page":"1248-1254","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of cardiac histology and cell death markers during the progression of diabetes in a streptozotocin\u2010induced diabetes rat model"],"prefix":"10.1002","volume":"9","author":[{"given":"Tamara","family":"S\u00e1ez","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Physiology Laboratory Universidad de Valpara\u00edso  Valpara\u00edso Chile"},{"name":"Department of Internal Medicine Universidad de Valpara\u00edso  Valpara\u00edso Chile"},{"name":"Center of Interdisciplinary Biomedical and Engineering Research for Health (MEDING) Universidad de Valpara\u00edso  Valpara\u00edso Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Carrasco\u2010Wong","sequence":"additional","affiliation":[{"name":"Cellular Signaling and Differentiation Laboratory (CSDL), School of Medical Technology, Medicine and Science Faculty Universidad San Sebasti\u00e1n  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Varas","sequence":"additional","affiliation":[{"name":"Center of Interdisciplinary Biomedical and Engineering Research for Health (MEDING) Universidad de Valpara\u00edso  Valpara\u00edso Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n San","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Center of Interdisciplinary Biomedical and Engineering Research for Health (MEDING) Universidad de Valpara\u00edso  Valpara\u00edso Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime A.","family":"Riquelme","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Farmacol\u00f3gica y Toxicol\u00f3gica, Faculty of Chemical and Pharmaceutical Sciences Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5493-0735","authenticated-orcid":false,"given":"Rienzi","family":"D\u00edaz\u2010Navarro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Physiology Laboratory Universidad de Valpara\u00edso  Valpara\u00edso Chile"},{"name":"Department of Internal Medicine Universidad de Valpara\u00edso  Valpara\u00edso Chile"},{"name":"Center of Interdisciplinary Biomedical and Engineering Research for Health (MEDING) Universidad de Valpara\u00edso  Valpara\u00edso Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01301-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.20960\/nh.1434"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0728-6"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(72)90595-4"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311586"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2020.05.009"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0014"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2019.02.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153319is"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00042"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.17179\/excli2018-1353"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2024213"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12497"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.001941"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.17179\/excli2022-5720"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8054073"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0681"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115843"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112412"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00174.2021"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0549"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.50"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-13-68"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S82272"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2020.1815170"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-6-6"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.07.129"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.474650"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.02.012"}],"container-title":["Animal 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