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Beta-adrenergic agonism protects mitochondrial metabolism in the pancreatectomised rat heart.
Lindsay, Ross T; Thisted, Louise; Zois, Nora E; Thrane, Sebastian T; West, James A; Fosgerau, Keld; Griffin, Julian L; Fink, Lisbeth N; Murray, Andrew J.
Afiliação
  • Lindsay RT; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. rosstlindsay@gmail.com.
  • Thisted L; Gubra A/S, Hørsholm Kongevej 11B, 2970, Hørsholm, Denmark. rosstlindsay@gmail.com.
  • Zois NE; Department of Biochemistry and Systems Biology Centre, University of Cambridge, Cambridge, UK. rosstlindsay@gmail.com.
  • Thrane ST; Gubra A/S, Hørsholm Kongevej 11B, 2970, Hørsholm, Denmark.
  • West JA; Gubra A/S, Hørsholm Kongevej 11B, 2970, Hørsholm, Denmark.
  • Fosgerau K; Ascendis Pharma A/S, Hellerup, Denmark.
  • Griffin JL; Gubra A/S, Hørsholm Kongevej 11B, 2970, Hørsholm, Denmark.
  • Fink LN; Department of Biochemistry and Systems Biology Centre, University of Cambridge, Cambridge, UK.
  • Murray AJ; AstraZeneca, Cambridge, UK.
Sci Rep ; 14(1): 19383, 2024 08 21.
Article em En | MEDLINE | ID: mdl-39169098
ABSTRACT
The diabetic heart is characterised by functional, morphological and metabolic alterations predisposing it to contractile failure. Chronic sympathetic activation is a feature of the pathogenesis of heart failure, however the type 1 diabetic heart shows desensitisation to ß-adrenergic stimulation. Here, we sought to understand the impact of repeated isoprenaline-mediated ß-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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Agonistas Adrenérgicos beta / Isoproterenol Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Agonistas Adrenérgicos beta / Isoproterenol Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article