The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes

被引：14

作者：

Marques, Catarina ^{[1
,2
]}

Goncalves, Andreia ^{[1
,2
]}

Ribeiro Pereira, Patricia Manuela ^{[1
,2
]}

Almeida, Daniela ^{[1
,2
]}

Martins, Beatriz ^{[1
,2
,3
]}

Fontes-Ribeiro, Carlos ^{[1
,2
,3
]}

Reis, Flavio ^{[1
,2
,3
]}

Fernandes, Rosa ^{[1
,2
,3
]}

机构：

[1] Univ Coimbra, Fac Med, Inst Pharmacol & Expt Therapeut, P-3000548 Coimbra, Portugal

[2] Univ Coimbra, Fac Med, Coimbra Inst Clin & Biomed Res iCBR, P-3000548 Coimbra, Portugal

[3] Univ Coimbra, CNCIBILI Consortium, Coimbra, Portugal

来源：

LIFE SCIENCES | 2019年 / 234卷

关键词：

Diabetic nephropathy; Type; 1; diabetes; Sitagliptin; Oxidative stress; Antioxidant defenses; Dipeptidyl peptidase-4; BLOOD-RETINAL BARRIER; IV; NEPHROPATHY; GLUCOSE; KIDNEY; APOPTOSIS; PREVENTS; DISEASE; INJURY; COMPLICATIONS;

D O I：

10.1016/j.lfs.2019.116738

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Aims: Oxidative stress has been linked to the development and progression of diabetic nephropathy (DN). The present study evaluated whether the dipeptidyl peptidase-4 inhibitor sitagliptin attenuates glomerular lesions and oxidative stress evoked by chronic hyperglycemia, by a mechanism independent of insulin secretion and glycemia normalization. Main methods: A rat model of DN caused by streptozotocin injection was established and the effects of sitagliptin (5 mg/kg/day) were evaluated after two weeks of treatment. Key findings: Sitagliptin treatment did not change body weight, glycemic and lipid profiles. However, histopathological observation revealed that sitagliptin attenuates diabetes-induced glomerular lesions on diabetic rats. Sitagliptin also ameliorated the increase in DPP-4 content and promoted the stabilization of GLP-1 in the diabetic kidney. Furthermore, sitagliptin treatment significantly attenuated the increase of free-radical formation and the decrease of antioxidant defenses, attenuating therefore the oxidative stress in the kidneys of diabetic animals. Significance: The results suggest that sitagliptin treatment alleviates kidney oxidative stress in type 1 diabetic rats, which could play a key role in reducing the progression of DN.

引用

页数：9

共 70 条

[1] Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes [J].