title: Diabetic nephropathy in a nonobese mouse model of type 2 diabetes mellitus.
abstract: A large body of research has contributed to our understanding of the pathophysiology of diabetic nephropathy. Yet, many questions remain regarding the progression of a disease that accounts for nearly half the patients entering dialysis yearly. Several murine models of diabetic nephropathy secondary to Type 2 diabetes mellitus (T2DM) do exist, and some are more representative than others, but all have limitations. In this study, we aimed to identify a new mouse model of diabetic nephropathy secondary to T2DM in a previously described T2DM model, the MKR (MCK-KR-hIGF-IR) mouse. In this mouse model, T2DM develops as a result of functional inactivation of insulin-like growth factor-1 receptor (IGF-1R) in the skeletal muscle. These mice are lean, with marked insulin resistance, hyperinsulinemia, hyperglycemia, and dyslipidemia and thus are representative of nonobese human T2DM. We show that the MKR mice, when under stress (high-fat diet or unilateral nephrectomy), develop progressive diabetic nephropathy with marked albuminuria and meet the histopathological criteria as defined by the Animal Models of Diabetic Complications Consortium. Finally, these MKR mice are fertile and are on a common background strain, making it a novel model to study the progression of diabetic nephropathy.
authors.affiliation: Dept. of Medicine/Nephrology, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1243, New York, NY. cijiang.he@mssm.edu.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Mallipattu
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Gallagher
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
authors.forename: Ruijie
authors.initials: R
authors.lastname: Liu
authors.forename: Anita
authors.initials: A
authors.lastname: Mehrotra
authors.forename: Sylvia J
authors.initials: SJ
authors.lastname: Horne
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chuang
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Yang
authors.forename: John C
authors.initials: JC
authors.lastname: He
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000209:etiology / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D050171:Dyslipidemias / Q000097:blood / Q000209:etiology / Q000235:genetics; D005298:Fertility; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009392:Nephrectomy; D010641:Phenotype; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin
keywords: Type 2 diabetes mellitus; diabetic nephropathy; insulin-like growth factor-I receptor; leptin