Reduction of cardiac and renal dysfunction by new inhibitor of DPP4 in diabetic rats

被引：5

作者：

Alves, Bryelle E. O. ^{[1
]}

de Alencar, Allan K. N. ^{[2
]}

Gamba, Luis E. R. ^{[2
]}

Trachez, Margarete M. ^{[2
]}

da Silva, Jaqueline S. ^{[2
]}

Araujo, Josenildo S. C. ^{[2
]}

Montagnoli, Tadeu L. ^{[2
]}

Mendes, Luiza V. P. ^{[2
]}

Pimentel-Coelho, Pedro M. ^{[3
]}

Cunha, Valeria do M. N. ^{[2
]}

Mendez-Otero, Rosalia ^{[3
]}

Oliveira, Glaucia M. M. ^{[1
]}

Lima, Lidia M. ^{[2
]}

Barreiro, Eliezer J. ^{[2
]}

Sudo, Roberto T. ^{[2
]}

Zapata-Sudo, Gisele ^{[2
]}

机构：

[1] Univ Fed Rio de Janeiro, Inst Coracao Edson Saad, Rio De Janeiro, Brazil

[2] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Rio De Janeiro, Brazil

[3] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, Brazil

来源：

PHARMACOLOGICAL REPORTS | 2019年 / 71卷 / 06期

关键词：

Type; 2; diabetes; Left ventricular diastolic dysfunction; Renal dysfunction; Dipeptidyl dipeptidase-4 inhibitor; Hypercaloric diet; Endothelial dysfunction; Metabolic disturbance; ENDOTHELIAL DYSFUNCTION; FATTY-ACIDS; SITAGLIPTIN; RECEPTOR; HYPERGLYCEMIA; HYPERTENSION; NEPHROPATHY; INSULIN; INJURY; CARDIOMYOPATHY;

D O I：

10.1016/j.pharep.2019.07.005

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (C) 2019 Published by Elsevier B.V.

引用

页码：1190 / 1200

页数：11

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