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Chronic sympathetic activation is a feature of the pathogenesis of heart failure, however the type 1 diabetic heart shows desensitisation to \u03b2-adrenergic stimulation. Here, we sought to understand the impact of repeated isoprenaline-mediated \u03b2-stimulation upon cardiac mitochondrial respiratory capacity and substrate metabolism in the 90% pancreatectomy (Px) rat model of type 1 diabetes. We hypothesised these hearts would be relatively protected against the metabolic impact of stress-induced cardiomyopathy. We found that individually both Px and isoprenaline suppressed cardiac mitochondrial respiration, but that this was preserved in Px rats receiving isoprenaline. Px and isoprenaline had contrasting effects on cardiac substrate metabolism, with increased reliance upon cardiac fatty acid oxidation capacity and altered ketone metabolism in the hearts of Px rats, but enhanced capacity for glucose uptake and metabolism in isoprenaline-treated rats. Moreover, Px rats were protected against isoprenaline-induced mortality, whilst isoprenaline elevated cGMP and protected myocardial energetic status in Px rat hearts. Our work suggests that adrenergic stimulation may be protective in the type 1 diabetic heart, and underlines the importance of studying pathological features in combination when modeling complex disease in rodents.<\/jats:p>","DOI":"10.1038\/s41598-024-70335-4","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T15:30:52Z","timestamp":1724340652000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Beta-adrenergic agonism protects mitochondrial metabolism in the pancreatectomised rat heart"],"prefix":"10.1038","volume":"14","author":[{"given":"Ross T.","family":"Lindsay","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Thisted","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora E.","family":"Zois","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian T.","family":"Thrane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"West","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keld","family":"Fosgerau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian L.","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisbeth N.","family":"Fink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"70335_CR1","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1056\/NEJMoa1408214","volume":"371","author":"M Lind","year":"2014","unstructured":"Lind, M. et al. 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RTL undertook a temporary, unpaid secondment with Gubra ApS at this time. RTL is currently an employee and shareholder of Rejuveron AG and declares no other potential or perceived conflicts of interest. NEZ is currently an employee and shareholder of Ascendis Pharma A\/S and declares no potential or perceived conflicts of interest. LNF is currently an employee of Ferring Pharmaceuticals A\/S and declares no further potential or perceived conflicts of interest. KF is currently an employee and shareholder of Pephexia Therapeutics and declares no further potential or perceived conflicts of interest.  JAW is currently an employee of AstraZeneca, and declares no further potential or perceived conflicts of interest. JLG and AJM declare that no conflicts of interest exist.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19383"}}