{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T01:51:44Z","timestamp":1785808304709,"version":"3.56.0"},"reference-count":72,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T00:00:00Z","timestamp":1613260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL091071"],"award-info":[{"award-number":["HL091071"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL107200"],"award-info":[{"award-number":["HL107200"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX001963"],"award-info":[{"award-number":["BX001963"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX000783"],"award-info":[{"award-number":["BX000783"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX005229"],"award-info":[{"award-number":["BX005229"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The obesity epidemic has increased type II diabetes mellitus (T2DM) across developed countries. Cardiac T2DM risks include ischemic heart disease, heart failure with preserved ejection fraction, intolerance to ischemia\u2010reperfusion (I\u2010R) injury, and refractoriness to cardioprotection. While opioids are cardioprotective, T2DM causes opioid receptor signaling dysfunction. We tested the hypothesis that sustained opioid receptor stimulus may overcome diabetes mellitus\u2010induced cardiac dysfunction via membrane\/mitochondrial\u2010dependent protection. In a murine T2DM model, we investigated effects of morphine on cardiac function, I\u2010R tolerance, ultrastructure, subcellular cholesterol expression, mitochondrial protein abundance, and mitochondrial function. T2DM induced 25% weight gain, hyperglycemia, glucose intolerance, cardiac hypertrophy, moderate cardiac depression, exaggerated postischemic myocardial dysfunction, abnormalities in mitochondrial respiration, ultrastructure and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010induced swelling, and cell death were all evident. Morphine administration for 5 days: (1) improved glucose homeostasis; (2) reversed cardiac depression; (3) enhanced I\u2010R tolerance; (4) restored mitochondrial ultrastructure; (5) improved mitochondrial function; (6) upregulated Stat3 protein; and (7) preserved membrane cholesterol homeostasis. These data show that morphine treatment restores contractile function, ischemic tolerance, mitochondrial structure and function, and membrane dynamics in type II diabetic hearts. These findings suggest potential translational value for short\u2010term, but high\u2010dose morphine administration in diabetic patients undergoing or recovering from acute ischemic cardiovascular events.\n                  <\/jats:p>","DOI":"10.1096\/fj.201903233r","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T13:06:54Z","timestamp":1613308014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Morphine induces physiological, structural, and molecular benefits in the diabetic myocardium"],"prefix":"10.1096","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-9343","authenticated-orcid":false,"given":"Alice E.","family":"Zemljic\u2010Harpf","sequence":"first","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-205X","authenticated-orcid":false,"given":"Louise E.","family":"See Hoe","sequence":"additional","affiliation":[{"name":"Department of Faculty of Medicine University of Queensland Brisbane QLD Australia"},{"name":"Critical Care Research Group The Prince Charles Hospital Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Schilling","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Zuniga\u2010Hertz","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Nguyen","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash J.","family":"Vaishnav","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna J.","family":"Belza","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris P.","family":"Budiono","sequence":"additional","affiliation":[{"name":"Heart Foundation Research Centre, Griffith Health Institute Griffith University Southport QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush M.","family":"Patel","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Head","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang H.","family":"Dillmann","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Medicine University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushil K.","family":"Mahata","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Medicine University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason N.","family":"Peart","sequence":"additional","affiliation":[{"name":"Heart Foundation Research Centre, Griffith Health Institute Griffith University Southport QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Roth","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Headrick","sequence":"additional","affiliation":[{"name":"Heart Foundation Research Centre, Griffith Health Institute Griffith University Southport QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6722-9625","authenticated-orcid":false,"given":"Hemal H.","family":"Patel","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System San Diego CA USA"},{"name":"Department of Anesthesiology University of California San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,14]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"142","article-title":"The epidemic of obesity and diabetes: trends and treatments","volume":"38","author":"Barnes AS","year":"2011","journal-title":"Tex Heart Inst J"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60460-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.10029"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00618-8"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-010-9131-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3171-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.113.008300"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0874"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)01161-X"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020904"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2007.02.080"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-11-67"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.13.1282"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)39092-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0907"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1288-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.172593"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(88)90010-X"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)37653-0"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.5.559"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(97)00631-0"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)80930-3"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00233.2006"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2004.03.038"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/jpm.2012.0270"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/imj.12857"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-007-0389-6"},{"key":"e_1_2_10_29_1","first-page":"H2157","article-title":"Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts","volume":"268","author":"Schultz JE","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00280.2007"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01279.2006"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072278"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/416254"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00548.2011"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(83)80379-9"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00728-07"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.02.011"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-215798"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-015-2316-3"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.027441"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2011.09.007"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.138"},{"key":"e_1_2_10_43_1","volume-title":"Fuels: aerobic and anaerobic metabolism","author":"Opie L","year":"2004"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.02.001"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.160"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13009"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083174"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201300026"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-825763"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.03.06.db05-0934"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2008-0345"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.075267"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-100107182"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2010.06.011"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1128294"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05837"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05904"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-009-1222-6"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2005.01.010"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.110460"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-12-36"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.138008"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.02.024"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9836302"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00150"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116942"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00081.2014"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2019.04.005"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1982.tb39501.x"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1580"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00406.2011"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01102.2006"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00135.2013"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201903233R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201903233R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201903233R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T21:27:51Z","timestamp":1761686871000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201903233R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,14]]},"references-count":72,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1096\/fj.201903233R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201903233r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,14]]},"assertion":[{"value":"2019-12-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21407"}}