{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T14:17:56Z","timestamp":1788013076865,"version":"build-2784847793"},"reference-count":56,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Cancer cachexia is a metabolic syndrome commonly observed in patients with pancreatic ductal adenocarcinoma (PDAC), characterized by wasting of skeletal and cardiac muscle. This condition is associated with the neurohormonal stress response and activation of the sympathetic nervous system. However the impact of cachexia on cardiac adrenergic signalling remains poorly understood. Here we used a preclinical model of PDAC cachexia to investigate how sympathetic input to the heart is altered. We found desensitization of \u03b21\u2010adrenergic receptor (\u03b21\u2010AR) in the heart, along with evidence of increased adrenergic tone. Pharmacological blockade with the \u03b21\u2010selective antagonist metoprolol partially restored adrenergic responsiveness in PDAC mice, suggesting that elevated adrenergic drive contributes to \u03b21\u2010AR desensitization. The impaired \u03b21\u2010AR sensitivity blunted the chronotropic response to dobutamine and reduced inotropic reserve under adrenergic stress. Together these findings uncover disruption of cardiac adrenergic signalling in PDAC cachexia.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70723-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Pancreatic cancer\u2010associated cachexia promotes \u03b21\u2010adrenergic receptor desensitization in the heart.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pancreatic cancer\u2010induced \u03b21\u2010adrenergic receptor desensitization is partly mediated by increased adrenergic transmission to the heart.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\u03b21\u2010adrenergic receptor desensitization in mice with pancreatic cancer reduces contractile reserve under adrenergic stress.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290616","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:24:31Z","timestamp":1784283871000},"page":"6281-6301","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pancreatic cancer cachexia promotes cardiac dysfunction through altered adrenergic signalling in the heart"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1014-510X","authenticated-orcid":false,"given":"Parham","family":"Diba","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Levasseur","sequence":"additional","affiliation":[{"name":"Department of Radiation Medicine Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3926-7709","authenticated-orcid":false,"given":"Samuel D.","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khia Min 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