title: Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals.
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 blood HbA1c levels 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 and HbA1c (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-1β and TNF-α levels, 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.
authors.affiliation: 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.
authors.forename: Catarina
authors.identifier: 0000-0003-4011-9586
authors.initials: C
authors.lastname: Marques
authors.affiliation: 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 ; ESAV, Technologies and Health Study Center, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal ; Educational Technologies and Health Study Center, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mega
authors.affiliation: 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.
authors.forename: Andreia
authors.initials: A
authors.lastname: Gonçalves
authors.affiliation: Institute of Immunology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal ; Immunology and Oncology Laboratory, CNC, 3004-517 Coimbra, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Rodrigues-Santos
authors.affiliation: 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 ; ESAV, Technologies and Health Study Center, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal.
authors.forename: Edite
authors.identifier: 0000-0002-6346-8319
authors.initials: E
authors.lastname: Teixeira-Lemos
authors.affiliation: 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.
authors.forename: Frederico
authors.initials: F
authors.lastname: Teixeira
authors.affiliation: 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.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fontes-Ribeiro
authors.affiliation: 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.
authors.forename: Flávio
authors.initials: F
authors.lastname: Reis
authors.affiliation: 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 ; Center of Ophthalmology and Vision Sciences, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D011924:Rats, Zucker; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D052216:Glucagon-Like Peptide 1; D000068900:Sitagliptin Phosphate