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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

2014Journal article Open access
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dc.contributor.authorMega, C.
dc.contributor.authorVala, Helena
dc.contributor.authorRodrigues-Santos, P.
dc.contributor.authorOliveira, J.
dc.contributor.authorTeixeira, F.
dc.contributor.authorFernandes, R.
dc.contributor.authorReis, F.
dc.contributor.authorLemos, ET
dc.date.accessioned2015-03-23T10:47:57Z
dc.date.available2015-03-23T10:47:57Z
dc.date.issued2014
dc.description.abstractBACKGROUND: 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 metabolicparameters, 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 diabeticanimals; 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.por
dc.description.sponsorshipThe Portuguese Foundation for Science and Technology (FCT) through the projects PEst-C/SAU/UI3282/2013 and PEst-OE/CED/UI4016/2014, and the Center for Studies in Education, Technologies and Health (CI&DETS) and PROTEC grant by the Polytechnic Institute of Viseu (IPV)por
dc.identifier.citationMega, C., Vala, H., Rodrigues-Santos, P., Oliveira, J., Teixeira, F., Fernandes, R., … de Lemos, E. T. (2014). 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. Diabetology & Metabolic Syndrome, 6(1), 42. http://doi.org/10.1186/1758-5996-6-42por
dc.identifier.doi10.1186/1758-5996-6-42
dc.identifier.urihttp://hdl.handle.net/10400.19/2724
dc.language.isoengpor
dc.peerreviewedyespor
dc.relation.publisherversionhttp://www.ncbi.nlm.nih.gov/pubmed/24650557por
dc.subjectType 2 diabetespor
dc.subjectEndocrine and exocrine pancreas lesionspor
dc.subjectSitagliptinpor
dc.subjectCytoprotective propertiespor
dc.subjectZDF ratpor
dc.titleSitagliptin prevents aggravation of endocrine and exocrine pancreatic damage in the Zucker Diabetic Fatty rat - focus on amelioration of metabolic profile and tissue cytoprotective propertiespor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage62por
oaire.citation.startPage62por
oaire.citation.titleDiabetology & Metabolic Syndromepor
oaire.citation.volume6(1)por
person.familyNameVala Correia
person.givenNameHelena Maria
person.identifier.ciencia-id7A1E-E85E-FFA4
person.identifier.orcid0000-0001-6829-4867
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublicationcdc3d2e2-df06-40ed-8900-1ecbc8a06c8a
relation.isAuthorOfPublication.latestForDiscoverycdc3d2e2-df06-40ed-8900-1ecbc8a06c8a

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