دورية أكاديمية
Reduction of cardiac and renal dysfunction by new inhibitor of DPP4 in diabetic rats.
| العنوان: | Reduction of cardiac and renal dysfunction by new inhibitor of DPP4 in diabetic rats. |
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| المؤلفون: | Alves BEO; Instituto do Coração Edson Saad, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., de Alencar AKN; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Gamba LER; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Trachez MM; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., da Silva JS; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Araújo JSC; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Montagnoli TL; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Mendes LVP; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Pimentel-Coelho PM; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., do M N Cunha V; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Mendez-Otero R; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Oliveira GMM; Instituto do Coração Edson Saad, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Lima LM; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Barreiro EJ; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Sudo RT; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Zapata-Sudo G; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: gsudo@icb.ufrj.br. |
| المصدر: | Pharmacological reports : PR [Pharmacol Rep] 2019 Dec; Vol. 71 (6), pp. 1190-1200. Date of Electronic Publication: 2019 Jul 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer International Publishing Country of Publication: Switzerland NLM ID: 101234999 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2299-5684 (Electronic) Linking ISSN: 17341140 NLM ISO Abbreviation: Pharmacol Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : Cham, Switzerland : Springer International Publishing Original Publication: Kraków, Poland : Institute of Pharmacology, Polish Academy of Sciences, c2005- |
| مواضيع طبية MeSH: | Dipeptidyl Peptidase 4/*metabolism , Dipeptidyl-Peptidase IV Inhibitors/*pharmacology , Heart/*drug effects , Kidney Diseases/*drug therapy, Animals ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Glucagon-Like Peptide 1/metabolism ; Kidney Diseases/metabolism ; Male ; Rats ; Rats, Wistar ; Sitagliptin Phosphate/pharmacology ; Streptozocin/pharmacology ; Ventricular Dysfunction, Left/drug therapy ; Ventricular Dysfunction, Left/metabolism |
| مستخلص: | Background: Increased mortality due to type 2 diabetes mellitus (T2DM) has been associated with renal and/or cardiovascular dysfunction. Dipeptidyl dipeptidase-4 inhibitors (iDPP-4s) may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms. In this study, the pharmacological profile of a new iDPP-4 (LASSBio-2124) was investigated in rats with cardiac and renal dysfunction induced by T2DM. Methods: T2DM was induced in rats by 2 weeks of a high-fat diet followed by intravenous injection of streptozotocin. Metabolic disturbance and cardiac, vascular, and renal dysfunction were analyzed in the experimental groups. Results: Sitagliptin and LASSBio-2124 administration after T2DM induction reduced elevated glucose levels to 319.8 ± 13.2 and 279.7 ± 17.8 mg/dL, respectively (p < 0.05). LASSBio-2124 also lowered the cholesterol and triglyceride levels from 76.8 ± 8.0 to 42.7 ± 3.2 mg/dL and from 229.7 ± 25.4 to 100.7 ± 17.1 mg/dL, in diabetic rats. Sitagliptin and LASSBio-2124 reversed the reduction of the plasma insulin level. LASSBio-2124 recovered the increased urinary flow in diabetic animals and reduced 24-h proteinuria from 23.7 ± 1.5 to 13.3 ± 2.8 mg (p < 0.05). It also reduced systolic and diastolic left-ventricular dysfunction in hearts from diabetic rats. Conclusion: The effects of LASSBio-2124 were superior to those of sitagliptin in the cardiovascular systems of T2DM rats. This new prototype showed promise for the avoidance of comorbidities in a T2DM experimental model, and thus may constitute an innovative therapeutic agent for the treatment of these conditions in the clinical field in future. (Copyright © 2019. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: Dipeptidyl dipeptidase-4 inhibitor; Endothelial dysfunction; Hypercaloric diet; Left ventricular diastolic dysfunction; Metabolic disturbance; Renal dysfunction; Type 2 diabetes |
| المشرفين على المادة: | 0 (Dipeptidyl-Peptidase IV Inhibitors) 5W494URQ81 (Streptozocin) 89750-14-1 (Glucagon-Like Peptide 1) EC 3.4.14.5 (Dipeptidyl Peptidase 4) TS63EW8X6F (Sitagliptin Phosphate) |
| تواريخ الأحداث: | Date Created: 20191101 Date Completed: 20200427 Latest Revision: 20240229 |
| رمز التحديث: | 20240229 |
| DOI: | 10.1016/j.pharep.2019.07.005 |
| PMID: | 31669883 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2299-5684 |
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| DOI: | 10.1016/j.pharep.2019.07.005 |