TY - JOUR
T1 - The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes
AU - Marques, Catarina
AU - Gonçalves, Andreia
AU - Pereira, Patrícia Manuela Ribeiro
AU - Almeida, Daniela
AU - Martins, Beatriz
AU - Fontes-Ribeiro, Carlos
AU - Reis, Flávio
AU - Fernandes, Rosa
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Antioxidant defenses
KW - Diabetic nephropathy
KW - Dipeptidyl peptidase-4
KW - Oxidative stress
KW - Sitagliptin
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85070581533&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2019.116738
DO - 10.1016/j.lfs.2019.116738
M3 - Article
C2 - 31398418
AN - SCOPUS:85070581533
SN - 0024-3205
VL - 234
JO - Life Sciences
JF - Life Sciences
M1 - 116738
ER -