Diabetic nephropathy amelioration by a low-dose sitagliptin in an animal model of type 2 diabetes (Zucker diabetic fatty rat).
This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl peptidase 4 inhibitor, on metabolic profile and on renal lesions aggravation in a rat model of type-2 diabetic nephropathy, the Zucker diabetic fatty (ZDF) rat. Diabetic and obese ZDF (fa/fa) rats and their controls ZDF (+/+) were treated for 6 weeks with vehicle (control) or sitagliptin (10 mg/kg/bw). Blood/serum glucose, HbA1c, insulin, Total-c, TGs, urea, and creatinine were assessed, as well as kidney glomerular and tubulointerstitial lesions (interstitial fibrosis/tubular atrophy), using a semiquantitative rating from 0 (absent/normal) to 3 (severe and extensive damage). Vascular lesions were scored from 0-2. Sitagliptin in the diabetic rats promoted an amelioration of glycemia, HbA1c, Total-c, and TGs, accompanied by a partial prevention of insulinopenia. Furthermore, together with urea increment prevention, renal lesions were ameliorated in the diabetic rats, including glomerular, tubulointerstitial, and vascular lesions, accompanied by reduced lipid peroxidation. In conclusion, chronic low-dose sitagliptin treatment was able to ameliorate diabetic nephropathy, which might represent a key step forward in the management of T2DM and this serious complication.
Laboratory of Pharmacology & Experimental Therapeutics, Institute for Biomedical Research on Light and Image (IBILI), Medicine Faculty, Coimbra University, 3000-548 Coimbra, Portugal.
Cristina
C
Mega
Edite Teixeira
ET
de Lemos
Helena
H
Vala
Rosa
R
Fernandes
Jorge
J
Oliveira
Filipa
F
Mascarenhas-Melo
Frederico
F
Teixeira
Flávio
F
Reis
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000097:blood; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications*; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011924:Rats, Zucker; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D008055:Lipids; D011719:Pyrazines; D014230:Triazoles; D000068900:Sitagliptin Phosphate