Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals
This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF) rat: 20-week-old rats were treated with sitagliptin...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/538737 |
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| author | Catarina Marques Cristina Mega Andreia Gonçalves Paulo Rodrigues-Santos Edite Teixeira-Lemos Frederico Teixeira Carlos Fontes-Ribeiro Flávio Reis Rosa Fernandes |
| author_facet | Catarina Marques Cristina Mega Andreia Gonçalves Paulo Rodrigues-Santos Edite Teixeira-Lemos Frederico Teixeira Carlos Fontes-Ribeiro Flávio Reis Rosa Fernandes |
| author_sort | Catarina Marques |
| collection | DOAJ |
| description | This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF) rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp.) and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1β and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties. |
| format | Article |
| id | doaj-art-2ab63d8c1cb444a3a366a918ef7998f1 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-2ab63d8c1cb444a3a366a918ef7998f12025-08-20T03:54:42ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/538737538737Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic AnimalsCatarina Marques0Cristina Mega1Andreia Gonçalves2Paulo Rodrigues-Santos3Edite Teixeira-Lemos4Frederico Teixeira5Carlos Fontes-Ribeiro6Flávio Reis7Rosa Fernandes8Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalLaboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalLaboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalInstitute of Immunology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalLaboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalLaboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalLaboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalLaboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalLaboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, PortugalThis study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF) rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp.) and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1β and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.http://dx.doi.org/10.1155/2014/538737 |
| spellingShingle | Catarina Marques Cristina Mega Andreia Gonçalves Paulo Rodrigues-Santos Edite Teixeira-Lemos Frederico Teixeira Carlos Fontes-Ribeiro Flávio Reis Rosa Fernandes Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals Mediators of Inflammation |
| title | Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals |
| title_full | Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals |
| title_fullStr | Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals |
| title_full_unstemmed | Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals |
| title_short | Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals |
| title_sort | sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals |
| url | http://dx.doi.org/10.1155/2014/538737 |
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