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

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Citações na Scopus
0
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BMC
Autores
RODRIGUES, Eder Anderson
ROSA, Camila Moreno
CAMPOS, Dijon Henrique Salome
DAMATTO, Felipe Cesar
SOUZA, Lidiane Moreira
PAGAN, Luana Urbano
GATTO, Mariana
BROSLER, Jessica Yumi
SOUZA, Hebreia Oliveira Almeida
Citação
DIABETOLOGY & METABOLIC SYNDROME, v.15, n.1, article ID 223, 13p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
BackgroundSodium-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.
Palavras-chave
SGLT2 inhibitors, Streptozotocin, Papillary muscle, Ventricular function, Myocardial metabolomics, Echocardiogram
URI
https://observatorio.fm.usp.br/handle/OPI/57867
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/29
Artigos e Materiais de Revistas Científicas - ODS/03