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Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects

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Resumo:Objective: 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 T2DM, the Zucker Diabetic Fatty (ZDF) rat. Methods: ZDF rats (aged 20 weeks) were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia, HbA1c, urea and creatinine levels were monitored. Kidney glomerular and tubulointerstitial lesions were assessed using a semiquantitative rating. Kidney mRNA and/or protein content of DPP-IV, GLP-1, TNF-α, IL-1β, BAX, Bcl-2 and Bid were evaluated by RT-PCR and/or WB. Protein distribution was evaluated by immunohistochemistry. Results: Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c, and prevented the diabetes-induced increase in DPP-IV levels and decrease in GLP-1 levels. Sitagliptin ameliorated diabetes-induced glomerular atrophy and IFTA, and the increased urea levels. Sitagliptin decreased kidney IL-1β and TNF-α, and prevented the increase of BAX/Bcl-2 ratio and Bid protein levels, which indicates protective effects against inflammation and pro-apoptotic state in the kidney of diabetic rats, respectively. Conclusion: Sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and anti-apoptotic properties.
Autores principais:Marques, C.
Outros Autores:Mega, C.; Gonçalves, A.; Rodrigues-Santos, P.; Vala, Helena; Teixeira-Lemos, E.; Teixeira, F.; Fontes-Ribeiro, C.; Reis, F.; Fernandes, R.
Assunto:sitagliptin Zucker Diabetic Fatty (ZDF) rat animal model of T2DM dipeptidyl peptidase IV (DPP-IV) inhibitor
Ano:2014
País:Portugal
Tipo de documento:documento de conferência
Tipo de acesso:acesso restrito
Instituição associada:Instituto Politécnico de Viseu
Idioma:inglês
Origem:Repositório Científico do Instituto Politécnico de Viseu
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author Marques, C.
author2 Mega, C.
Gonçalves, A.
Rodrigues-Santos, P.
Vala, Helena
Teixeira-Lemos, E.
Teixeira, F.
Fontes-Ribeiro, C.
Reis, F.
Fernandes, R.
author2_role author
author
author
author
author
author
author
author
author
author_facet Marques, C.
Mega, C.
Gonçalves, A.
Rodrigues-Santos, P.
Vala, Helena
Teixeira-Lemos, E.
Teixeira, F.
Fontes-Ribeiro, C.
Reis, F.
Fernandes, R.
author_role author
contributor_name_str_mv Instituto Politécnico de Viseu
country_str PT
creators_json_str [{\"Person.name\":\"Marques, C.\"},{\"Person.name\":\"Mega, C.\"},{\"Person.name\":\"Gonçalves, A.\"},{\"Person.name\":\"Rodrigues-Santos, P.\"},{\"Person.name\":\"Vala, Helena\",\"Person.identifier.orcid\":\"0000-0001-6829-4867\"},{\"Person.name\":\"Teixeira-Lemos, E.\"},{\"Person.name\":\"Teixeira, F.\"},{\"Person.name\":\"Fontes-Ribeiro, C.\"},{\"Person.name\":\"Reis, F.\"},{\"Person.name\":\"Fernandes, R.\"}]
datacite.contributors.contributor.contributorName.fl_str_mv Instituto Politécnico de Viseu
datacite.creators.creator.creatorName.fl_str_mv Marques, C.
Mega, C.
Gonçalves, A.
Rodrigues-Santos, P.
Vala, Helena
Teixeira-Lemos, E.
Teixeira, F.
Fontes-Ribeiro, C.
Reis, F.
Fernandes, R.
datacite.date.Accepted.fl_str_mv 2014-01-01T00:00:00Z
datacite.date.available.fl_str_mv 2015-03-23T10:08:22Z
datacite.date.embargoed.fl_str_mv 2015-03-23T10:08:22Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_16ec
datacite.subjects.subject.fl_str_mv sitagliptin
Zucker Diabetic Fatty (ZDF) rat
animal model of T2DM
dipeptidyl peptidase IV (DPP-IV) inhibitor
datacite.titles.title.fl_str_mv Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
dc.contributor.none.fl_str_mv Instituto Politécnico de Viseu
dc.creator.none.fl_str_mv Marques, C.
Mega, C.
Gonçalves, A.
Rodrigues-Santos, P.
Vala, Helena
Teixeira-Lemos, E.
Teixeira, F.
Fontes-Ribeiro, C.
Reis, F.
Fernandes, R.
dc.date.Accepted.fl_str_mv 2014-01-01T00:00:00Z
dc.date.available.fl_str_mv 2015-03-23T10:08:22Z
dc.date.embargoed.fl_str_mv 2015-03-23T10:08:22Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10400.19/2715
dc.language.none.fl_str_mv eng
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_16ec
dc.subject.none.fl_str_mv sitagliptin
Zucker Diabetic Fatty (ZDF) rat
animal model of T2DM
dipeptidyl peptidase IV (DPP-IV) inhibitor
dc.title.fl_str_mv Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_c94f
description Objective: 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 T2DM, the Zucker Diabetic Fatty (ZDF) rat. Methods: ZDF rats (aged 20 weeks) were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia, HbA1c, urea and creatinine levels were monitored. Kidney glomerular and tubulointerstitial lesions were assessed using a semiquantitative rating. Kidney mRNA and/or protein content of DPP-IV, GLP-1, TNF-α, IL-1β, BAX, Bcl-2 and Bid were evaluated by RT-PCR and/or WB. Protein distribution was evaluated by immunohistochemistry. Results: Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c, and prevented the diabetes-induced increase in DPP-IV levels and decrease in GLP-1 levels. Sitagliptin ameliorated diabetes-induced glomerular atrophy and IFTA, and the increased urea levels. Sitagliptin decreased kidney IL-1β and TNF-α, and prevented the increase of BAX/Bcl-2 ratio and Bid protein levels, which indicates protective effects against inflammation and pro-apoptotic state in the kidney of diabetic rats, respectively. Conclusion: Sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and anti-apoptotic properties.
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oai_identifier_str oai:repositorio.ipv.pt:10400.19/2715
organization_str_mv urn:organizationAcronym:ripv
person_str_mv Marques, C.
Mega, C.
Gonçalves, A.
Rodrigues-Santos, P.
Vala, Helena
Vala, Helena
https://www.ciencia-id.pt/7A1E-E85E-FFA4
7A1E-E85E-FFA4
http://orcid.org/0000-0001-6829-4867
0000-0001-6829-4867
Teixeira-Lemos, E.
Teixeira, F.
Fontes-Ribeiro, C.
Reis, F.
Fernandes, R.
publishDate 2014
reponame_str Repositório Científico do Instituto Politécnico de Viseu
repository_id_str urn:repositoryAcronym:ripv
service_str_mv urn:repositoryAcronym:ripv
spelling engporObjective: 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 T2DM, the Zucker Diabetic Fatty (ZDF) rat. Methods: ZDF rats (aged 20 weeks) were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia, HbA1c, urea and creatinine levels were monitored. Kidney glomerular and tubulointerstitial lesions were assessed using a semiquantitative rating. Kidney mRNA and/or protein content of DPP-IV, GLP-1, TNF-α, IL-1β, BAX, Bcl-2 and Bid were evaluated by RT-PCR and/or WB. Protein distribution was evaluated by immunohistochemistry. Results: Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c, and prevented the diabetes-induced increase in DPP-IV levels and decrease in GLP-1 levels. Sitagliptin ameliorated diabetes-induced glomerular atrophy and IFTA, and the increased urea levels. Sitagliptin decreased kidney IL-1β and TNF-α, and prevented the increase of BAX/Bcl-2 ratio and Bid protein levels, which indicates protective effects against inflammation and pro-apoptotic state in the kidney of diabetic rats, respectively. Conclusion: Sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and anti-apoptotic properties.application/pdfporSitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effectsMarques, C.Mega, C.Gonçalves, A.Rodrigues-Santos, P.PersonalVala, HelenaDSpacehttp://dspace.org/items/cdc3d2e2-df06-40ed-8900-1ecbc8a06c8aDSpacehttp://dspace.org/items/cdc3d2e2-df06-40ed-8900-1ecbc8a06c8aVala CorreiaHelena MariaCiência IDhttps://www.ciencia-id.pt7A1E-E85E-FFA4ORCIDhttp://orcid.org0000-0001-6829-4867Teixeira-Lemos, E.Teixeira, F.Fontes-Ribeiro, C.Reis, F.Fernandes, R.HostingInstitutionOrganizationalInstituto Politécnico de Viseue-mailmailto:repositorio@sc.ipv.ptrepositorio@sc.ipv.pt2015-03-23T10:08:22Z20142014-01-01T00:00:00ZHandlehttp://hdl.handle.net/10400.19/2715http://purl.org/coar/access_right/c_16ecrestricted accesssitagliptinZucker Diabetic Fatty (ZDF) ratanimal model of T2DMdipeptidyl peptidase IV (DPP-IV) inhibitor1729316 bytesother research producthttp://purl.org/coar/resource_type/c_c94fconference objecthttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ipv.pt/bitstreams/89582d94-8dbd-4812-9dd9-707367b1c7c6/downloadVirchows Arch465 (Supll I)
spellingShingle Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
Marques, C.
sitagliptin
Zucker Diabetic Fatty (ZDF) rat
animal model of T2DM
dipeptidyl peptidase IV (DPP-IV) inhibitor
subject.fl_str_mv sitagliptin
Zucker Diabetic Fatty (ZDF) rat
animal model of T2DM
dipeptidyl peptidase IV (DPP-IV) inhibitor
title Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
title_full Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
title_fullStr Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
title_full_unstemmed Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
title_short Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
title_sort Sitagliptin ameliorates kidney lesions in a rat model of type 2 diabetes due to anti-inflammatory and anti-apoptotic effects
topic sitagliptin
Zucker Diabetic Fatty (ZDF) rat
animal model of T2DM
dipeptidyl peptidase IV (DPP-IV) inhibitor
topic_facet sitagliptin
Zucker Diabetic Fatty (ZDF) rat
animal model of T2DM
dipeptidyl peptidase IV (DPP-IV) inhibitor
url http://hdl.handle.net/10400.19/2715
visible 1