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

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.