Pathogenesis and treatment of type 2 diabetic nephropathy: lessons from the spontaneous KK/Ta mouse model.
Diabetic nephropathy is a major cause of end-stage renal failure (ESRF) in patients with both type 1 and type 2 diabetes. Many factors such as genetic and non-genetic promoters, hypertension, hyperglycemia, accumulation of advanced glycation end products (AGEs), dyslipidemia, albuminuria and proteinuria influence the progression of this disease. It is important to determine pathogenesis and treatment of this disease. However, it is difficult to investigate since human diabetes is a heterogeneous and multifactorial disease. Therefore, most of these mechanisms have been investigated in animal experiments. KK/Ta mice have a clearly different genetic background in terms of body weight, blood glucose, impaired glucose tolerance (IGT), urinary albumin excretion and serum triglyceride than BALB/c mice. Renal lesions of KK/Ta mice closely resemble those in human early diabetic nephropathy. Thus, the KK/Ta mouse may serve as a suitable model for the study of type 2 diabetes and early diabetic nephropathy in humans. We reviewed genetic susceptibility using genome-wide linkage analysis and differential display polymerase chain reaction (DD-PCR) or Northern blot analysis, and treatment of diabetic nephropathy using angiotensin type 1 (AT1) receptor blockers (ARB) or thiazolidinediones (TZDs) in KK/Ta mice.
Tomino
Yasuhiko
Y
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan. yasu@med.juntendo.ac.jp
Tanimoto
Mitsuo
M
Shike
Toshihide
T
Shiina
Kenji
K
Fan
Qiuling
Q
Liao
Jie
J
Gohda
Tomohito
T
Makita
Yuichiro
Y
Funabiki
Kazuhiko
K
D000419:Albuminuria / Q000235:genetics; D000818:Animals; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger