ArticleDiabetology & metabolic syndrome2014
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.
Article in Diabetology & metabolic syndrome, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Sitagliptin Mitigates Diabetic Cardiomyopathy Through Oxidative Stress Reduction and Suppression of VEGF and FLT-1 Expression in Rats.Biomolecules · 2025Article
- Cymbopogon proximus Chiov's extract improves insulin sensitivity in rats with dexamethasone-induced insulin resistance and underlying mechanisms.Scientific reports · 2025Article
- The antidiabetic effect of safflower yellow by regulating the GOAT/ghrelin/GHS-R1a/cAMP/TRPM2 pathway.Scientific reports · 2025Article
- Exploring the therapeutic potential ofVeterinary world · 2024Article
- DPP-4 Inhibitors: Renoprotective Potential and Pharmacokinetics in Type 2 Diabetes Mellitus Patients with Renal Impairment.European journal of drug metabolism and pharmacokinetics · 2020Review
- Article
- DPP-4 Inhibitor Sitagliptin Improves Cardiac Function and Glucose Homeostasis and AmelioratesJournal of diabetes research · 2018Article
- Therapeutic Options Targeting Oxidative Stress, Mitochondrial Dysfunction and Inflammation to Hinder the Progression of Vascular Complications of Diabetes.Frontiers in physiology · 2018Review
- Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes.Journal of diabetes research · 2017Review
- DPP-4 inhibition improves early mortality, β cell function, and adipose tissue inflammation in db/db mice fed a diet containing sucrose and linoleic acid.Diabetology & metabolic syndrome · 2016Article
- Immuno-modulator metallo-Peptide reduces inflammatory state in obese zucker fa/fa rats.International journal of biomedical science : IJBS · 2014Article
- Effect of dipeptidyl peptidase 4 inhibitors on acute and subacute models of inflammation in male Wistar rats: An experimental study.International journal of applied & basic medical researchArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
methodsMale 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.
resultsSitagliptin 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.
conclusionIn 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.