Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109393
DC Field | Value | Language |
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dc.contributor.author | Mega, Cristina | - |
dc.contributor.author | Vala, Helena | - |
dc.contributor.author | Rodrigues-Santos, Paulo | - |
dc.contributor.author | Oliveira, Jorge | - |
dc.contributor.author | Teixeira, Frederico | - |
dc.contributor.author | Fernandes, Rosa | - |
dc.contributor.author | Reis, F. | - |
dc.contributor.author | Lemos, Edite Teixeira de | - |
dc.date.accessioned | 2023-10-12T09:41:57Z | - |
dc.date.available | 2023-10-12T09:41:57Z | - |
dc.date.issued | 2014-03-20 | - |
dc.identifier.issn | 1758-5996 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/109393 | - |
dc.description.abstract | Background: The purpose of this study was to investigate some of the possible mechanisms underlying the protective effects of a dipeptidyl peptidase IV (DPP-IV) inhibitor, sitagliptin, on pancreatic tissue in an animal model of type 2 diabetes mellitus (T2DM), the Zucker Diabetic Fatty (ZDF) rat, focusing on glycaemic, insulinic and lipidic profiles, as well as, on apoptosis, inflammation, angiogenesis and proliferation mediators. Methods: Male obese diabetic ZDF (fa/fa) rats, aged 20 weeks, were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks and compared to untreated diabetic and lean control littermates. Metabolic data was evaluated at the beginning and at the end of the treatment, including glycaemia, HbA1c, insulinaemia, HOMA-beta and TGs. Endocrine and exocrine pancreas lesions were assessed semiquantitatively by histopathological methods. Pancreas gene (mRNA) and protein expression of mediators of apoptotic machinery, inflammation and angiogenesis/ proliferation (Bax, Bcl2, IL-1β, VEGF, PCNA and TRIB3) were analyzed by RT-qPCR and/or by immunohistochemistry. Results: Sitagliptin treatment for 6 weeks (between 20 and 26 week-old) was able to significantly (p < 0.001) ameliorate all the metabolic parameters, by preventing the increase in blood glucose and in serum TGs contents (16.54% and 37.63%, respectively, vs untreated), as well as, by preventing the decrease in serum insulin levels and in the functional beta cells capacity accessed via HOMA-beta index (156.28% and 191.74%, respectively, vs untreated). Sitagliptin-treated diabetic rats presented a reduced pancreas Bax/Bcl2 ratio, suggestive of an antiapoptotic effect; in addition, sitagliptin was able to completely reduce (p < 0.001) the pancreas overexpression of IL-1β and TRIB3 found in the untreated diabetic animals; and promoted a significant (p < 0.001) overexpression of VEGF and PCNA. Conclusion: In this animal model of obese T2DM (the ZDF rat), sitagliptin prevented β-cell dysfunction and evolution of pancreatic damage. The protective effects afforded by this DPP-IV inhibitor may derive from improvement of the metabolic profile (viewed by the amelioration of glucose and TGs levels and of insulin resistance) and from cytoprotective properties, such as antiapoptotic, anti-inflammatory, pro-angiogenic and pro-proliferative. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | PEst-C/SAU/UI3282/2013 | pt |
dc.relation | PEst-OE/CED/UI4016/2014 | pt |
dc.relation | Center for Studies in Education, Technologies and Health (CI&DETS) | pt |
dc.relation | PROTEC grant by the Polytechnic Institute of Viseu (IPV) | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Type 2 diabetes | pt |
dc.subject | Endocrine and exocrine pancreas lesions | pt |
dc.subject | Sitagliptin | pt |
dc.subject | Cytoprotective properties | pt |
dc.subject | ZDF rat | pt |
dc.title | Sitagliptin prevents aggravation of endocrine and exocrine pancreatic damage in the Zucker Diabetic Fatty rat - focus on amelioration of metabolic profile and tissue cytoprotective properties | pt |
dc.type | article | - |
degois.publication.firstPage | 42 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Diabetology and Metabolic Syndrome | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1186/1758-5996-6-42 | pt |
degois.publication.volume | 6 | pt |
dc.date.embargo | 2014-03-20 | * |
uc.date.periodoEmbargo | 0 | pt |
item.fulltext | Com Texto completo | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
crisitem.project.grantno | Strategic Project - UI 3282 - 2013-2014 | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | ICBR Coimbra Institute for Clinical and Biomedical Research | - |
crisitem.author.parentresearchunit | Faculty of Medicine | - |
crisitem.author.orcid | 0000-0002-2601-0923 | - |
crisitem.author.orcid | 0000-0001-7828-2296 | - |
crisitem.author.orcid | 0000-0003-3401-9554 | - |
crisitem.author.orcid | 0000-0002-6346-8319 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais I&D IBILI - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais |
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