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The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes.
Life Sci. 2019 Oct 01; 234:116738.LS

Abstract

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.

Authors+Show Affiliations

Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal.Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal.Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal.Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal. Electronic address: rcfernandes@fmed.uc.pt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31398418

Citation

Marques, Catarina, et al. "The Dipeptidyl Peptidase 4 Inhibitor Sitagliptin Improves Oxidative Stress and Ameliorates Glomerular Lesions in a Rat Model of Type 1 Diabetes." Life Sciences, vol. 234, 2019, p. 116738.
Marques C, Gonçalves A, Pereira PMR, et al. The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes. Life Sci. 2019;234:116738.
Marques, C., Gonçalves, A., Pereira, P. M. R., Almeida, D., Martins, B., Fontes-Ribeiro, C., Reis, F., & Fernandes, R. (2019). The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes. Life Sciences, 234, 116738. https://doi.org/10.1016/j.lfs.2019.116738
Marques C, et al. The Dipeptidyl Peptidase 4 Inhibitor Sitagliptin Improves Oxidative Stress and Ameliorates Glomerular Lesions in a Rat Model of Type 1 Diabetes. Life Sci. 2019 Oct 1;234:116738. PubMed PMID: 31398418.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2019/08/06/ PY - 2019/02/04/received PY - 2019/07/29/revised PY - 2019/08/05/accepted PY - 2019/8/10/pubmed PY - 2019/9/21/medline PY - 2019/8/10/entrez KW - Antioxidant defenses KW - Diabetic nephropathy KW - Dipeptidyl peptidase-4 KW - Oxidative stress KW - Sitagliptin KW - Type 1 diabetes SP - 116738 EP - 116738 JF - Life sciences JO - Life Sci VL - 234 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/31398418/The_dipeptidyl_peptidase_4_inhibitor_sitagliptin_improves_oxidative_stress_and_ameliorates_glomerular_lesions_in_a_rat_model_of_type_1_diabetes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30665-4 DB - PRIME DP - Unbound Medicine ER -