Cited by 126Diabetes Treatment and ManagementChronic Kidney Disease and DiabetesAcute Kidney Injury Research

The DOI matches its Crossref record; 74 of the 80 references it cites were found in a registry or an index.

Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals

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Marques, Catarina, Mega, Cristina, Gonçalves, Andreia, Rodrigues-Santos, Paulo, Teixeira-Lemos, Edite, Teixeira, Frederico, Fontes-Ribeiro, Carlos, Reis, Flávio, Fernandes, Rosa·2014·Mediators of Inflammation

Abstract

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 type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF) rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia and bloodHbA1clevels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia andHbA1c(by about 22.5% and 1.2%, resp.) and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1βand TNF-αlevels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.

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  1. 10.1038/ncpendmet0894 · DOI
  2. 2007, Kidney International, S49
  3. 2000, Journal of the American Society of Nephrology, 11, 1656, 10.1681/ASN.V1191656 · DOI
  4. 2000, Kidney International, 58, S3
  5. 10.2337/diabetes.55.1.225 · DOI
  6. 2003, American Journal of Physiology: Renal Physiology, 284, F455
  7. 10.2337/dc06-0703 · DOI
  8. 10.1152/ajprenal.00288.2005 · DOI
  9. 1999, Journal of Nephrology, 12, 159
  10. 10.1159/000025912 · DOI
  11. 1999, Current Medicinal Chemistry, 6, 311, 10.2174/0929867306666220208213543 · DOI
  12. 2013, Kidney International, 85, 579
  13. 2012, PLoS ONE, 7
  14. 2003, Kidney International, 64, S64
  15. 10.1046/j.1523-1755.2001.059002415.x · DOI
  16. 2011, Histology and Histopathology, 26, 1599
  17. 10.1210/en.2009-1166 · DOI

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Metadata

Authors
Marques, C., Mega, C., Gonçalves, A., Rodrigues-Santos, P., Teixeira-Lemos, E., Teixeira, F., Fontes-Ribeiro, C., Reis, F., & Fernandes, R.
Affiliations
  • University of Coimbra (PT)
  • Centro de Estudos em Educação Tecnologia e Saúde (PT)
  • Institute of Immunology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
  • Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
Corresponding author
Fernandes, Rosa
Venue
Mediators of Inflammation
Publisher
Wiley
Published
2014
Volume
2014
Pages
1-15
ISSN
  • 0962-9351 (ISSN-L)
  • 1466-1861
OpenAlex
W2105771613
Cited by
126
References
80
Citations by year
2026: 5 · 2025: 2 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 15 · 2020: 15 · 2019: 10 · 2018: 11 · 2017: 21 · 2016: 15 · 2015: 8 · 2014: 1
FWCI
12.07
Type
journal article
Language
en
Open access
Locations
  • Mediators of Inflammation (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
Funders
Foundation for Science and Technology, Portugal (PEst-C/SAU/UI3282/2011, PEst-C/SAU/UI3282/2013, COMPETE)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
sitagliptin, type 2 diabetes, diabetic nephropathy, DPP-4 inhibitors, glucagon-like peptide-1, GLP-1 receptor, renal inflammation, apoptosis, Bax/Bcl-2 ratio, Bid, TNF-α, IL-1β, tubulointerstitial injury, glomerular lesions, glycemic control, Zucker diabetic fatty rats
MeSH terms
Sitagliptin Phosphate, Animals, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Inflammation, Kidney, Pyrazines, Rats, Zucker, Triazoles, Tumor Necrosis Factor-alpha, Apoptosis, Rats, Glucagon-Like Peptide 1, Dipeptidyl-Peptidase IV Inhibitors

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