{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T02:11:31Z","timestamp":1773454291236,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T00:00:00Z","timestamp":1670025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005007","name":"Asia University","doi-asserted-by":"publisher","award":["CMU107\u2010ASIA\u201008"],"award-info":[{"award-number":["CMU107\u2010ASIA\u201008"]}],"id":[{"id":"10.13039\/501100005007","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR\u2010111\u2010087"],"award-info":[{"award-number":["DMR\u2010111\u2010087"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR\u2010108\u2010057"],"award-info":[{"award-number":["DMR\u2010108\u2010057"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012544","name":"China Medical University, Taiwan","doi-asserted-by":"publisher","award":["CMU107\u2010ASIA\u201008"],"award-info":[{"award-number":["CMU107\u2010ASIA\u201008"]}],"id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012544","name":"China Medical University, Taiwan","doi-asserted-by":"publisher","award":["CMU109\u2010MF\u201076"],"award-info":[{"award-number":["CMU109\u2010MF\u201076"]}],"id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 106\u20102320\u2010B\u2010039\u2010016\u2010MY3"],"award-info":[{"award-number":["MOST 106\u20102320\u2010B\u2010039\u2010016\u2010MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetes\u2010induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin\u2010like growth factor II receptor \u03b1 (IGF\u2010IIR\u03b1) is a cardiac risk factor. In this study, we hypothesized IGF\u2010IIR\u03b1 could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague\u2013Dawley rat model with specific IGF\u2010IIR\u03b1 overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF\u2010IIR\u03b1 in diabetic hearts. The results showed that IGF\u2010IIR\u03b1 overexpression aided hyperglycemia in creating more myocardial injury. Pro\u2010inflammatory factors, such as Tumor necrosis factor\u2010alpha, Interleukin\u20106, Cyclooxygenase\u20102, Inducible nitric oxide synthase, and Nuclear factor\u2010kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac\u2010specific IGF\u2010IIR\u03b1 overexpression. Correspondingly, IGF\u2010IIR\u03b1 overexpression in the diabetic myocardium also reduced the PI3K\u2010AKT survival axis and activated mitochondrial\u2010dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac\u2010specific IGF\u2010IIR\u03b1 overexpression. Overall, all results provid clear evidence that IGF\u2010IIR\u03b1 can enhance cardiac damage and is a harmful factor to the heart under high\u2010blood glucose conditions. However, the pathophysiology of IGF\u2010IIR\u03b1 under different stresses and its downstream regulation in the heart still require further research.<\/jats:p>","DOI":"10.1002\/tox.23717","type":"journal-article","created":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T17:19:58Z","timestamp":1670087998000},"page":"676-684","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Insulin\u2010like growth factor <scp>II<\/scp> receptor alpha overexpression in heart aggravates hyperglycemia\u2010induced cardiac inflammation and myocardial necrosis"],"prefix":"10.1002","volume":"38","author":[{"given":"Chin\u2010Hu","family":"Lai","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Surgery, Department of Surgery Taichung Armed Force General Hospital  Taichung Taiwan"},{"name":"Graduate Institute of Medical Science China Medical University  Taichung Taiwan"},{"name":"Center of General Education is division National Defense Medical Center  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dao","family":"Van Thao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Science China Medical University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce Chi\u2010Kang","family":"Tsai","sequence":"additional","affiliation":[{"name":"Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis Jine\u2010Yuan","family":"Hsieh","sequence":"additional","affiliation":[{"name":"School of Medical Laboratory and Biotechnology Chung Shan Medical University  Taichung Taiwan"},{"name":"Clinical Laboratory Chung Shan Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Yu\u2010Chih","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2097-2240","authenticated-orcid":false,"given":"Wei\u2010Wen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, College of Life Sciences China Medical University  Taichung Taiwan"},{"name":"Ph.D. Program for Biotechnology Industry China Medical University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia\u2010Hua","family":"Kuo","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Biochemistry University of Taipei  Taipei Taiwan"},{"name":"Department of Kinesiology and Health Science College of William and Mary  Williamsburg Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang\u2010Yeh","family":"Lu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Science China Medical University  Taichung Taiwan"},{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine China Medical University Hospital  Taichung Taiwan"},{"name":"College of Medicine China Medical University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih\u2010Chieh","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, School of Medicine China Medical University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan\u2010Ho","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Medicine China Medical University  Taichung Taiwan"},{"name":"Department of Emergency Medicine China Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2347-0411","authenticated-orcid":false,"given":"Chih\u2010Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Science China Medical University  Taichung Taiwan"},{"name":"Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation  Hualien Taiwan"},{"name":"Department of Medical Research China Medical University Hospital  Taichung Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology Asia University  Taichung Taiwan"},{"name":"Center of General Education, Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology  Hualien Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.02.023"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1016"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.679597"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311586"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0938"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1385\/CT:5:3:285"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00509-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0242"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00088.2002"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00583.2005"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2011.08.008"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-6-30"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.10.2949"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01230-X"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000064682"},{"issue":"59","key":"e_1_2_10_17_1","first-page":"212","article-title":"Prevalence of diastolic dysfunction in type 2 diabetes mellitus","volume":"15","author":"Yadava S","year":"2017","journal-title":"Kathmandu Univ Med J"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00079.2019"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22676"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216285"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12845"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.46"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-020-02474-z"},{"key":"e_1_2_10_24_1","first-page":"1","article-title":"Hyperglycemia\u2010induced cardiac damage is alleviated by heat\u2010inactivated lactobacillus reuteri GMNL\u2010263 via activation of the IGF1R survival pathway. Probiotics and antimicrobial","volume":"13","author":"Koay K\u2010P","year":"2021","journal-title":"Proteins"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.109810"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-020-09668-1"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2020.104255"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-020-0432-x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.7603\/s40681-014-0019-9"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.7603\/s40681-014-0012-3"},{"key":"e_1_2_10_31_1","first-page":"e13666","article-title":"Resveratrol inhibited the metastatic behaviors of cisplatin\u2010resistant human oral cancer cells via phosphorylation of ERK\/p\u201038 and suppression of MMP\u20102\/9","author":"Chang WS","year":"2021","journal-title":"J Food Biochem"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.29219\/fnr.v66.8645"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-021-09929-8"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23153"},{"key":"e_1_2_10_35_1","first-page":"1","article-title":"Neuroprotective effects of probiotic lactobacillus reuteri GMNL\u2010263 in the hippocampus of Streptozotocin\u2010induced diabetic rats","author":"Lin J\u2010Y","year":"2022","journal-title":"Probiotic Antimicrobial Proteins"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-022-00544-0"},{"key":"e_1_2_10_37_1","first-page":"1299\u20101314","article-title":"Curcumin\u2010pretreated adipose\u2010derived stem cells enhance the neuroprotective ability to repair rheumatoid arthritis\u2010induced damage in the rat brain. The","author":"Ju D\u2010T","year":"2022","journal-title":"Am J Chinese Med"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22864"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22989"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23350"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23599"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/hjh.0000000000003285"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/2047487319878371"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28957"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203244"},{"key":"e_1_2_10_46_1","first-page":"2014:1\u20102","article-title":"Oxidative stress and inflammation in diabetic complications","author":"Vikram A","year":"2014","journal-title":"Hindawi"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx011"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612824666180327165604"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23208"}],"container-title":["Environmental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.23717","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/tox.23717","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.23717","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T02:49:43Z","timestamp":1692413383000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tox.23717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,3]]},"references-count":48,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/tox.23717"],"URL":"https:\/\/doi.org\/10.1002\/tox.23717","archive":["Portico"],"relation":{},"ISSN":["1520-4081","1522-7278"],"issn-type":[{"value":"1520-4081","type":"print"},{"value":"1522-7278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,3]]},"assertion":[{"value":"2022-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}