Standardization of type 1 and type 2 diabetic nephropathy models in rats: Assessment and characterization of metabolic features and renal injury.
Diabetic nephropathy
nicotinamide
rat model
streptozotocin
type 1 diabetes mellitus
type 2 diabetes mellitus
Journal
Journal of pharmacy & bioallied sciences
ISSN: 0976-4879
Titre abrégé: J Pharm Bioallied Sci
Pays: India
ID NLM: 101537209
Informations de publication
Date de publication:
Historique:
received:
28
10
2019
revised:
11
02
2020
accepted:
17
03
2020
entrez:
26
10
2020
pubmed:
27
10
2020
medline:
27
10
2020
Statut:
ppublish
Résumé
Diabetes mellitus and its complications, such as nephropathy, represent a global burden. Recent research focuses on developing drugs that specifically target the pathogenesis of diabetic nephropathy rather than merely treating hyperglycemia. Rodent models of animal disease are integral in drug discovery and represent an obligatory regulatory requirement. The aim of this study was to develop and standardize rat models of type 1 and type 2 diabetic nephropathy, resembling characteristics of human clinical condition. Rats were administered streptozotocin (STZ) 50 mg/kg intraperitoneally (i.p.), and STZ 50 mg/kg i.p. + nicotinamide (NA) 110 mg/kg i.p., for induction of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), respectively. Metabolic parameters (body weight, feed and water intake, blood glucose, serum insulin, oral glucose tolerance test, intraperitoneal insulin tolerance test, and indices of insulin sensitivity) were evaluated to characterize the symptoms of T1DM and T2DM. Renal damage was confirmed by the estimation of renal function biomarkers, kidney antioxidant status, kidney hypertrophy index, and histopathology. STZ and STZ + NA administration increased blood glucose levels significantly. Metabolic parameters indicated that administration of STZ resulted in clinical features of human T1DM, whereas STZ + NA rats resembled human T2DM. STZ- and STZ + NA-treated rats developed diabetic nephropathy in 4 weeks, indicated by altered levels of renal function markers, increased kidney hypertrophy index, increased renal oxidative stress, and altered tissue architecture. The study proposes reproducible and cost-effective rat models for both T1DM- and T2DM-induced diabetic nephropathy characterized by stable metabolic features and typical renal lesions.
Sections du résumé
BACKGROUND
BACKGROUND
Diabetes mellitus and its complications, such as nephropathy, represent a global burden. Recent research focuses on developing drugs that specifically target the pathogenesis of diabetic nephropathy rather than merely treating hyperglycemia. Rodent models of animal disease are integral in drug discovery and represent an obligatory regulatory requirement.
AIM
OBJECTIVE
The aim of this study was to develop and standardize rat models of type 1 and type 2 diabetic nephropathy, resembling characteristics of human clinical condition.
MATERIALS AND METHODS
METHODS
Rats were administered streptozotocin (STZ) 50 mg/kg intraperitoneally (i.p.), and STZ 50 mg/kg i.p. + nicotinamide (NA) 110 mg/kg i.p., for induction of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), respectively. Metabolic parameters (body weight, feed and water intake, blood glucose, serum insulin, oral glucose tolerance test, intraperitoneal insulin tolerance test, and indices of insulin sensitivity) were evaluated to characterize the symptoms of T1DM and T2DM. Renal damage was confirmed by the estimation of renal function biomarkers, kidney antioxidant status, kidney hypertrophy index, and histopathology.
RESULTS
RESULTS
STZ and STZ + NA administration increased blood glucose levels significantly. Metabolic parameters indicated that administration of STZ resulted in clinical features of human T1DM, whereas STZ + NA rats resembled human T2DM. STZ- and STZ + NA-treated rats developed diabetic nephropathy in 4 weeks, indicated by altered levels of renal function markers, increased kidney hypertrophy index, increased renal oxidative stress, and altered tissue architecture. The study proposes reproducible and cost-effective rat models for both T1DM- and T2DM-induced diabetic nephropathy characterized by stable metabolic features and typical renal lesions.
Identifiants
pubmed: 33100790
doi: 10.4103/jpbs.JPBS_239_19
pii: JPBS-12-295
pmc: PMC7574755
doi:
Types de publication
Journal Article
Langues
eng
Pagination
295-307Informations de copyright
© 2020 Journal of Pharmacy and Bioallied Sciences.
Déclaration de conflit d'intérêts
There are no conflicts of interest.
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