{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T07:39:59Z","timestamp":1781336399111,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,8,28]],"date-time":"2009-08-28T00:00:00Z","timestamp":1251417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Increased myocyte apoptosis in diabetic hearts has been previously reported. Therefore, the purpose of this study was to evaluate the effects of insulin on cardiac apoptotic, hypertrophic, and survival pathways in streptozotocin (STZ)\u2010induced diabetic rats. Forty\u2010eight male Wistar rats at 8 weeks of age were randomly divided into control group (Control), STZ\u2010induced (65\u2009mg\/kg STZ i.v.) Type 1\u2010like diabetic rats (DM), and DM rats with 4\u2009IU insulin replacement (DI) for 4 and 8 weeks, respectively. The levels of protein involved in cardiac apoptotic, hypertrophic, and survival pathways were measured by Western blotting. Cardiac mitochondrial\u2010dependent apoptotic pathways, such as Bad, cytosolic cytochrome <jats:italic>c<\/jats:italic>, activated caspase 9 and 3, and calcineurin\u2010nuclear factor activation transcription 3 (NFAT3) hypertrophic pathway in DM were increased compared to Control and attenuated in DI group after 8 weeks whereas those were not found after 4 weeks. Cardiac anti\u2010apoptotic Bcl2 and phosphorylated\u2010Bad were significantly decreased in DM group but not in DI group after 8 weeks. Insulin\u2010like growth factor\u2010I receptor (IGFIR), phosphatidylinositol 3'\u2010kinase (PI3K), and the protein kinase B (Akt) were significantly decreased in DM relative to Control and DI after 8 weeks whereas those were not found after 4 weeks. Insulin replacement not only prevents activation of the cardiac mitochondrial\u2010dependent apoptotic pathway and calcineurin\u2010related NFAT3 hypertrophic pathway in diabetes but it also enhances the cardiac insulin\/IGFIR\u2013PI3K\u2013Akt survival pathway, all of which are attenuated with insulin therapeutic duration\u2010dependent manners. The findings may provide possible diabetes\u2010related apoptotic, hypertrophic, and survival pathways for potentially preventing cardiac abnormality in diabetes. Copyright \u00a9 2009 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cbf.1601","type":"journal-article","created":{"date-parts":[[2009,8,28]],"date-time":"2009-08-28T04:24:52Z","timestamp":1251433492000},"page":"479-487","source":"Crossref","is-referenced-by-count":24,"title":["Effects of insulin replacement on cardiac apoptotic and survival pathways in streptozotocin\u2010induced diabetic rats"],"prefix":"10.1002","volume":"27","author":[{"given":"Wei\u2010Wen","family":"Kuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Ching","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Tzu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih\u2010Ping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia\u2010Hua","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuu\u2010Jen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010Hai","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Chi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Yang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2010Da","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,8,28]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2007.07.002"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.11.013"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.8144"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.12.1123"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780057"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.11.1111"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00127.2005"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2006.03.064"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.3317\/jraas.2007.018"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-006-7028-4"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2005.05.046"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.7479"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(01)00032-7"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-5323(03)00031-9"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/bss0660017"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.017129"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10722"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(99)80069-6"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh1201.093159"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1244"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1358\/mf.2000.22.8.802271"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.1.154"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-571-8_22"},{"key":"e_1_2_1_26_2","first-page":"485","article-title":"Animal model of human disease. Diabetes mellitus","volume":"101","author":"Seemayer TA","year":"1980","journal-title":"Am J Pathol"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2002000900010"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1372.007"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00509-6"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00536.2003"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.2741\/1141"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-006-0017-7"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1662"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.2165\/00129784-200606050-00002"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.3132\/dvdr.2004.005"},{"key":"e_1_2_1_36_2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.14712\/fb2004050020058","article-title":"Cytopathological basis of heart failure\u2013cardiomyocyte apoptosis, interstitial fibrosis and inflammatory cell response","volume":"50","author":"Petrovic D","year":"2004","journal-title":"Folia Biol (Praha)"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202474099"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1139\/Y08-021"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00038.2005"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1311-5"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706684"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00003.2002"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcbf.1601","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.1601","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:25:18Z","timestamp":1760041518000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.1601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,28]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2009,10]]}},"alternative-id":["10.1002\/cbf.1601"],"URL":"https:\/\/doi.org\/10.1002\/cbf.1601","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"value":"0263-6484","type":"print"},{"value":"1099-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,28]]}}}