The influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus rats

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorRODRIGUES, Eder Anderson
dc.contributor.authorROSA, Camila Moreno
dc.contributor.authorCAMPOS, Dijon Henrique Salome
dc.contributor.authorDAMATTO, Felipe Cesar
dc.contributor.authorMURATA, Gilson Masahiro
dc.contributor.authorSOUZA, Lidiane Moreira
dc.contributor.authorPAGAN, Luana Urbano
dc.contributor.authorGATTO, Mariana
dc.contributor.authorBROSLER, Jessica Yumi
dc.contributor.authorSOUZA, Hebreia Oliveira Almeida
dc.contributor.authorMARTINS, Mario Machado
dc.contributor.authorBASTOS, Luciana Machado
dc.contributor.authorTANNI, Suzana Erico
dc.contributor.authorOKOSHI, Katashi
dc.contributor.authorOKOSHI, Marina Politi
dc.date.accessioned2024-02-15T14:39:33Z
dc.date.available2024-02-15T14:39:33Z
dc.date.issued2023
dc.description.abstractBackgroundSodium-glucose cotransporter (SGLT)2 inhibitors have displayed beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. As most clinical trials were performed in Type 2 DM, their effects in Type 1 DM have not been established.ObjectiveTo evaluate the influence of long-term treatment with SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, energy metabolism, and metabolomics in rats with Type 1 DM.MethodsMale Wistar rats were divided into groups: Control (C, n = 15); DM (n = 15); and DM treated with dapagliflozin (DM + DAPA, n = 15) for 30 weeks. DM was induced by streptozotocin. Dapagliflozin 5 mg/kg/day was added to chow. Statistical analysis: ANOVA and Tukey or Kruskal-Wallis and Dunn.ResultsDM + DAPA presented lower glycemia and higher body weight than DM. Echocardiogram showed DM with left atrium dilation and left ventricular (LV) hypertrophy, dilation, and systolic and diastolic dysfunction. In LV isolated papillary muscles, DM had reduced developed tension, +dT/dt and -dT/dt in basal condition and after inotropic stimulation. All functional changes were attenuated by dapagliflozin. Hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) activity was lower in DM than C, and PFK and PK activity higher in DM + DAPA than DM. Metabolomics revealed 21 and 5 metabolites positively regulated in DM vs. C and DM + DAPA vs. DM, respectively; 6 and 3 metabolites were negatively regulated in DM vs. C and DM + DAPA vs. DM, respectively. Five metabolites that participate in cell membrane ultrastructure were higher in DM than C. Metabolites levels of N-oleoyl glutamic acid, chlorocresol and N-oleoyl-L-serine were lower and phosphatidylethanolamine and ceramide higher in DM + DAPA than DM.ConclusionLong-term treatment with dapagliflozin attenuates cardiac remodeling, myocardial dysfunction, and contractile reserve impairment in Type 1 diabetic rats. The functional improvement is combined with restored pyruvate kinase and phosphofructokinase activity and attenuated metabolomics changes.eng
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipThe authors thank the Nanobiotechnology Laboratory, NANOBIO, and Prof. Luiz Ricardo Goulart (<italic>in memoriam</italic>) for collaboration in metabolomics.
dc.identifier.citationDIABETOLOGY & METABOLIC SYNDROME, v.15, n.1, article ID 223, 13p, 2023
dc.identifier.doi10.1186/s13098-023-01196-6
dc.identifier.eissn1758-5996
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/57867
dc.language.isoeng
dc.publisherBMCeng
dc.relation.ispartofDiabetology & Metabolic Syndrome
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright BMCeng
dc.subjectSGLT2 inhibitorseng
dc.subjectStreptozotocineng
dc.subjectPapillary muscleeng
dc.subjectVentricular functioneng
dc.subjectMyocardial metabolomicseng
dc.subjectEchocardiogrameng
dc.subject.otherheart-failureeng
dc.subject.otheroxidative stresseng
dc.subject.othern-acetylcysteineeng
dc.subject.otherfood restrictioneng
dc.subject.othercardiomyopathyeng
dc.subject.otherempagliflozineng
dc.subject.otherdysfunctioneng
dc.subject.othermuscleeng
dc.subject.otherphosphofructokinaseeng
dc.subject.otherdehydrogenaseeng
dc.subject.wosEndocrinology & Metabolismeng
dc.titleThe influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus ratseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalRODRIGUES, Eder Anderson:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalROSA, Camila Moreno:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalCAMPOS, Dijon Henrique Salome:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalDAMATTO, Felipe Cesar:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalSOUZA, Lidiane Moreira:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalPAGAN, Luana Urbano:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalGATTO, Mariana:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalBROSLER, Jessica Yumi:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalSOUZA, Hebreia Oliveira Almeida:Univ Fed Uberlandia, Inst Biotechnol, Lab Nanobiotechnol Prof Dr Luiz Ricardo Goulart, Uberlandia, MG, Brazil
hcfmusp.author.externalMARTINS, Mario Machado:Univ Fed Uberlandia, Inst Biotechnol, Lab Nanobiotechnol Prof Dr Luiz Ricardo Goulart, Uberlandia, MG, Brazil
hcfmusp.author.externalBASTOS, Luciana Machado:Univ Fed Uberlandia, Inst Biotechnol, Lab Nanobiotechnol Prof Dr Luiz Ricardo Goulart, Uberlandia, MG, Brazil
hcfmusp.author.externalTANNI, Suzana Erico:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalOKOSHI, Katashi:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.author.externalOKOSHI, Marina Politi:Sao Paulo State Univ UNESP, Botucatu Med Sch, Dept Internal Med, Botucatu, SP, Brazil
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcGILSON MASAHIRO MURATA
hcfmusp.description.articlenumber223
hcfmusp.description.issue1
hcfmusp.description.volume15
hcfmusp.origemWOS
hcfmusp.origem.pubmed37908006
hcfmusp.origem.scopus2-s2.0-85175708565
hcfmusp.origem.wosWOS:001090845800001
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hcfmusp.publisher.countryENGLANDeng
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