{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:05:31Z","timestamp":1792073131833,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81830022"],"award-info":[{"award-number":["81830022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970671"],"award-info":[{"award-number":["81970671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900789"],"award-info":[{"award-number":["81900789"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070319"],"award-info":[{"award-number":["82070319"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing","doi-asserted-by":"publisher","award":["7212127"],"award-info":[{"award-number":["7212127"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The role of cardiac microvascular endothelial cells (CMECs) in diabetic cardiomyopathy is not fully understood. We aimed to investigate whether a glucagon receptor (GCGR) monoclonal antibody (mAb) ameliorated diabetic cardiomyopathy and clarify whether and how CMECs participated in the process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Research Design and Methods<\/jats:title><jats:p>The <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice were treated with GCGR mAb or immunoglobulin G (as control) for 4\u2009weeks. Echocardiography was performed to evaluate cardiac function. Immunofluorescent staining was used to determine microvascular density. The proteomic signature in isolated primary CMECs was analyzed by using tandem mass tag\u2010based quantitative proteomic analysis. Some target proteins were verified by using western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with <jats:italic>db<\/jats:italic>\/<jats:italic>m<\/jats:italic> mice, cardiac microvascular density and left ventricular diastolic function were significantly reduced in <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice, and this reduction was attenuated by GCGR mAb treatment. A total of 199 differentially expressed proteins were upregulated in <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice versus <jats:italic>db<\/jats:italic>\/<jats:italic>m<\/jats:italic> mice and downregulated in GCGR mAb\u2010treated <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice versus <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice. The enrichment analysis demonstrated that fatty acid \u03b2\u2010oxidation and mitochondrial fusion were the key pathways. The changes of the related proteins carnitine palmitoyltransferase 1B, optic atrophy type 1, and mitofusin\u20101 were further verified by using western blot. The levels of these three proteins were upregulated in <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice, whereas this upregulation was attenuated by GCGR mAb treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GCGR antagonism has a protective effect on CMECs and cardiac diastolic function in diabetic mice, and this beneficial effect may be mediated via inhibiting fatty acid \u03b2\u2010oxidation and mitochondrial fusion in CMECs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.13458","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T23:12:11Z","timestamp":1692659531000},"page":"1081-1094","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fatty acid \u03b2\u2010oxidation and mitochondrial fusion are involved in cardiac microvascular endothelial cell protection induced by glucagon receptor antagonism in diabetic mice"],"prefix":"10.1111","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5636-671X","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"},{"name":"NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education Beijing Key Laboratory of Cardiovascular Receptors Research  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8838-703X","authenticated-orcid":false,"given":"Rui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaona","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongzhe","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism The Affiliated Hospital of Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6004-955X","authenticated-orcid":false,"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Zu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"},{"name":"NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education Beijing Key Laboratory of Cardiovascular Receptors Research  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5744-5129","authenticated-orcid":false,"given":"Tianpei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m997"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741\u2010018\u20109749\u20101"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010020\u20100339\u20102"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741\u2010013\u20109378\u20107"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016\u20101748"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00492.2002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz5346"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc\u20102019\u2010001025"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2019.05.030"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2017.1395020"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010018\u20101597\u20101"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201002011\u2010x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.147009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2020.170349"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104567"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2018.11.001"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010019\u20100806\u20104"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.065"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.03.148"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.039767"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.02.039"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky869"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.075978"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.08.001"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404156"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.398"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010018\u20100042\u20106"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.04.363"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4779"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010021\u201001366\u20108"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010022\u201001575\u20109"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010022\u201000409\u20103"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.12.005"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201000883\u20106"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.119.040180"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.037"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424\u2010012\u20101156\u20101"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/Jci23354"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007383200"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.01.013"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.01.014"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14\u20100874"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200611080"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvr002"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303554"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010015\u20100173\u20108"}],"container-title":["Journal of Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1753-0407.13458","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T09:41:00Z","timestamp":1705138860000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1753-0407.13458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,19]]},"references-count":49,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/1753-0407.13458"],"URL":"https:\/\/doi.org\/10.1111\/1753-0407.13458","archive":["Portico"],"relation":{},"ISSN":["1753-0393","1753-0407"],"issn-type":[{"value":"1753-0393","type":"print"},{"value":"1753-0407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,19]]},"assertion":[{"value":"2023-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}