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We aimed to investigate whether these changes are associated with downstream impairments in cAMP and Ca<jats:sup>2+<\/jats:sup> signalling in a type 1 diabetes (T1D)\u2010induced DCM model. T1D was induced in adult male rats by streptozotocin (65\u2009mg\/kg) injection. DCM was assessed by cardiac structural and molecular remodelling. We delineated sequential changes affecting the exchange protein (Epac1\/2), cAMP\u2010dependent protein kinase A (PKA) and Ca<jats:sup>2+<\/jats:sup>\/Calmodulin\u2010dependent kinase II (CaMKII) at 4, 8 and 12\u2009weeks following diabetes, by real\u2010time quantitative PCR and western blot. Expression of Ca<jats:sup>2+<\/jats:sup> ATPase pump (SERCA2a), phospholamban (PLB) and Troponin I (TnI) was also examined. Early upregulation of Epac1 transcripts was noted in diabetic hearts at Week 4, followed by increases in Epac2 mRNA, but not protein levels, at Week 12. Expression of PKA subunits (RI, RII\u03b1 and C\u03b1) remained unchanged regardless of the disease stage, whereas CaMKII increased at Week 12 in DCM. Moreover, PLB transcripts were upregulated in diabetic hearts, whereas SERCA2a and TnI gene expression was unchanged irrespective of the disease evolution. PLB phosphorylation at threonine\u201017 was increased in DCM, whereas phosphorylation of both PLB at serine\u201016 and TnI at serine\u201023\/24 was unchanged. We show for the first time differential and time\u2010specific regulations in cardiac cAMP effectors and Ca<jats:sup>2+<\/jats:sup> handling proteins, data that may prove useful in proposing new therapeutic approaches in T1D\u2010induced DCM.<\/jats:p>","DOI":"10.1111\/jcmm.17733","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T07:05:56Z","timestamp":1679900756000},"page":"1277-1289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential changes in cyclic adenosine 3\u2032\u20105\u2032 monophosphate (<scp>cAMP<\/scp>) effectors and major Ca<sup>2+<\/sup> handling proteins during diabetic cardiomyopathy"],"prefix":"10.1111","volume":"27","author":[{"given":"Victoria","family":"Chaoul","sequence":"first","affiliation":[{"name":"Gilbert and Rose\u2010Marie Chagoury School of Medicine Lebanese American University  P.O. 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