Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/109393
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
Authors: Mega, Cristina 
Vala, Helena
Rodrigues-Santos, Paulo 
Oliveira, Jorge
Teixeira, Frederico 
Fernandes, Rosa 
Reis, F. 
Lemos, Edite Teixeira de 
Keywords: Type 2 diabetes; Endocrine and exocrine pancreas lesions; Sitagliptin; Cytoprotective properties; ZDF rat
Issue Date: 20-Mar-2014
Publisher: Springer Nature
Project: PEst-C/SAU/UI3282/2013 
PEst-OE/CED/UI4016/2014 
Center for Studies in Education, Technologies and Health (CI&DETS) 
PROTEC grant by the Polytechnic Institute of Viseu (IPV) 
Serial title, monograph or event: Diabetology and Metabolic Syndrome
Volume: 6
Issue: 1
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.
URI: https://hdl.handle.net/10316/109393
ISSN: 1758-5996
DOI: 10.1186/1758-5996-6-42
Rights: openAccess
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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