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

التفاصيل البيبلوغرافية
العنوان: The influence of dapagliflozin on cardiac remodeling, myocardial function and metabolomics in type 1 diabetes mellitus rats.
المؤلفون: Rodrigues EA; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Rosa CM; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Campos DHS; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Damatto FC; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Murata GM; LIM29, Division of Nephrology, Medical School, University of Sao Paulo, USP, Sao Paulo, SP, Brazil., Souza LM; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Pagan LU; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Gatto M; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Brosler JY; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Souza HOA; Laboratory of Nanobiotechnology Prof. Dr. Luiz Ricardo Goulart, Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG, Brazil., Martins MM; Laboratory of Nanobiotechnology Prof. Dr. Luiz Ricardo Goulart, Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG, Brazil., Bastos LM; Laboratory of Nanobiotechnology Prof. Dr. Luiz Ricardo Goulart, Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG, Brazil., Tanni SE; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Okoshi K; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil., Okoshi MP; Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu, SP, Brazil. marina.okoshi@unesp.br.
المصدر: Diabetology & metabolic syndrome [Diabetol Metab Syndr] 2023 Oct 31; Vol. 15 (1), pp. 223. Date of Electronic Publication: 2023 Oct 31.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101488958 Publication Model: Electronic Cited Medium: Print ISSN: 1758-5996 (Print) Linking ISSN: 17585996 NLM ISO Abbreviation: Diabetol Metab Syndr Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central
مستخلص: Background: Sodium-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.
Objective: To 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.
Methods: Male 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.
Results: DM + 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.
Conclusion: Long-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.
(© 2023. The Author(s).)
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معلومات مُعتمدة: 140400/2019-2 CNPq - National Council for Scientific and Technological Development, Brazil; 307280/ 2022-5 CNPq - National Council for Scientific and Technological Development, Brazil; 307.703/2022-3 CNPq - National Council for Scientific and Technological Development, Brazil; 2021/10923-5 FAPESP - Research Support Foundation of the State of São Paulo, Brazil
فهرسة مساهمة: Keywords: Echocardiogram; Myocardial metabolomics; Papillary muscle; SGLT2 inhibitors; Streptozotocin; Ventricular function
تواريخ الأحداث: Date Created: 20231101 Latest Revision: 20231103
رمز التحديث: 20231103
مُعرف محوري في PubMed: PMC10617150
DOI: 10.1186/s13098-023-01196-6
PMID: 37908006
قاعدة البيانات: MEDLINE
الوصف
تدمد:1758-5996
DOI:10.1186/s13098-023-01196-6