Amelioration of Early Markers of Diabetic Nephropathy by Linagliptin in Fructose-Streptozotocin-Induced Type 2 Diabetic Rats.
Animals
Biomarkers
/ metabolism
Blood Glucose
/ metabolism
Diabetes Mellitus, Type 2
/ chemically induced
Diabetic Nephropathies
/ metabolism
Fructose
/ administration & dosage
Hypoglycemic Agents
/ pharmacology
Kidney Function Tests
Linagliptin
/ pharmacology
Male
Oxidative Stress
Rats
Rats, Wistar
Streptozocin
/ administration & dosage
Diabetic nephropathy
Fructose-streptozotocin
Kidney injury molecule-1
Linagliptin
Neutrophil gelatinase-associated lipocalin
Vanin-1
Journal
Nephron
ISSN: 2235-3186
Titre abrégé: Nephron
Pays: Switzerland
ID NLM: 0331777
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
08
2018
accepted:
13
11
2018
pubmed:
31
1
2019
medline:
1
1
2020
entrez:
31
1
2019
Statut:
ppublish
Résumé
Early prediction and clinical intervention are extremely important in order to delay or hinder diabetic nephropathy (DN) progression. This study aimed to detect early signs of DN and study the potential ameliorating effect of the dipeptidyl peptidase-4 inhibitor, linagliptin, on some early markers for DN in fructose-streptozotocin (Fr-STZ)-induced diabetic rats. Fr-STZ rats were treated with either linagliptin (3 mg/kg p.o. daily), metformin (350 mg/kg p.o. daily), or their combination for 6 weeks. Fr-STZ DN rats exhibited obvious tubular renal damage and glomerular podocyte injury as confirmed by renal kidney -injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and vanin-1 mRNA, as well as urinary N-acetyl-β-D-glucosaminidase elevation and nephrin mRNA suppression, associated with the appearance of marked renal interstitial fibrosis and glomerulosclerosis despite the absence of microalbuminuria. Initiation of oxidative, inflammatory, fibrotic, and apoptotic reactions was evident in the settings of renal hyperglycemia. Linagliptin significantly modulated the aforementioned renal tubular injury makers and restored glomerular nephrin expression as well as reversed renal histopathological alterations. Oxidative, inflammatory, fibrotic and apoptotic processes were also alleviated. This study suggests that linagliptin exerts renoprotection against early features of DN in rats probably by inhibition of high glucose-induced renal tubular and glomerular injury thereby hampering KIM-1 and NGAL as well as vanin-1 associated with renal inflammation, fibrosis and oxidative stress.
Sections du résumé
BACKGROUND
Early prediction and clinical intervention are extremely important in order to delay or hinder diabetic nephropathy (DN) progression.
OBJECTIVES
This study aimed to detect early signs of DN and study the potential ameliorating effect of the dipeptidyl peptidase-4 inhibitor, linagliptin, on some early markers for DN in fructose-streptozotocin (Fr-STZ)-induced diabetic rats.
METHOD
Fr-STZ rats were treated with either linagliptin (3 mg/kg p.o. daily), metformin (350 mg/kg p.o. daily), or their combination for 6 weeks.
RESULTS
Fr-STZ DN rats exhibited obvious tubular renal damage and glomerular podocyte injury as confirmed by renal kidney -injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and vanin-1 mRNA, as well as urinary N-acetyl-β-D-glucosaminidase elevation and nephrin mRNA suppression, associated with the appearance of marked renal interstitial fibrosis and glomerulosclerosis despite the absence of microalbuminuria. Initiation of oxidative, inflammatory, fibrotic, and apoptotic reactions was evident in the settings of renal hyperglycemia. Linagliptin significantly modulated the aforementioned renal tubular injury makers and restored glomerular nephrin expression as well as reversed renal histopathological alterations. Oxidative, inflammatory, fibrotic and apoptotic processes were also alleviated.
CONCLUSIONS
This study suggests that linagliptin exerts renoprotection against early features of DN in rats probably by inhibition of high glucose-induced renal tubular and glomerular injury thereby hampering KIM-1 and NGAL as well as vanin-1 associated with renal inflammation, fibrosis and oxidative stress.
Identifiants
pubmed: 30699409
pii: 000495517
doi: 10.1159/000495517
doi:
Substances chimiques
Biomarkers
0
Blood Glucose
0
Hypoglycemic Agents
0
Fructose
30237-26-4
Linagliptin
3X29ZEJ4R2
Streptozocin
5W494URQ81
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
273-286Informations de copyright
© 2019 S. Karger AG, Basel.