title: Mouse Models of Diabetes, Obesity and Related Kidney Disease.
abstract: Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly assigned to low-dose streptozotocin (STZ, 55 mg/kg/day, five consecutive days) or vehicle control, whereas HFD-fed mice were given either one high-dose of STZ (100 mg/kg) or vehicle control. Intraperitoneal glucose tolerance tests were performed at Week 14, 20 and 30. Urinary albumin to creatinine ratio (ACR) and serum creatinine were measured, and renal structure was assessed using Periodic Acid Schiff (PAS) staining at Week 32. Results showed that chow-fed mice exposed to five doses of STZ resembled type 1 diabetes mellitus with a lean phenotype, hyperglycaemia, microalbuminuria and increased serum creatinine levels. Their kidneys demonstrated moderate tubular injury with evidence of tubular dilatation and glycogenated nuclear inclusion bodies. HFD-fed mice resembled metabolic syndrome as they were obese with dyslipidaemia, insulin resistance, and significantly impaired glucose tolerance. One dose STZ, in addition to HFD, did not worsen metabolic features (including fasting glucose, non esterified fatty acid, and triglyceride levels). There were significant increases in urinary ACR and serum creatinine levels, and renal structural changes were predominantly related to interstitial vacuolation and tubular dilatation in HFD-fed mice.
authors: Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.|Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors: Sarah J
authors: SJ
authors: Glastras
authors: School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, Australia.
authors: Hui
authors: H
authors: Chen
authors: Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.
authors: Rachel
authors: R
authors: Teh
authors: Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors: Rachel T
authors: RT
authors: McGrath
authors: Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors: Jason
authors: J
authors: Chen
authors: Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.
authors: Carol A
authors: CA
authors: Pollock
authors: Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.
authors: Muh Geot
authors: MG
authors: Wong
authors: Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia.
authors: Sonia
authors: S
authors: Saad
mesh_terms: D000418:Albumins / Q000032:analysis; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D006801:Humans; D007668:Kidney / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D011897:Random Allocation; D013311:Streptozocin
chemical_list: D000418:Albumins; D001786:Blood Glucose; D013311:Streptozocin; D003404:Creatinine