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Fukami, K., Ueda, S., Yamagishi, S., Kato, S., Inagaki, Y., Takeuchi, M., Motoyama, Y., Bucala, R., Iida, S., Tamaki, K., Imaizumi, T. and Cooper, M.E. (2004) AGEs activate mesangial TGF-beta-smad signaling via an angiotensin II type I receptor interaction. Kidney International, 66, 2137-2147. doi:10.1111/j.1523-1755.2004.66004.x

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• TITLE: Podocyte loss and albuminuria of KK-Ay mouse: A spontaneous animal model for human type 2 diabetic nephropathy

  AUTHORS: Yuji Ishikawa, Takamichi Ito, Mitsuo Tanimoto, Shinji Hagiwara, Masako Furukawa, Saori Yamaguchi, Keisuke Omote, Katsuhiko Asanuma, Tomohito Gohda, Yoshio Shimizu, Kazuhiko Funabiki, Satoshi Horikoshi, Yasuhiko Tomino

  KEYWORDS: Podocyte Loss; Albuminuria; Diabetic Rodent Model; Diabetes Type 2; DiabeticNephropathy

  JOURNAL NAME: Journal of Diabetes Mellitus, Vol.2 No.3, August 31, 2012

  ABSTRACT: Podocyte loss was well known in type 2 diabetic nephropathy patients. The objective of the present study was to determine the number of podocytes and the degree of albuminuria in diabetic KK-Ay/Ta (KK-Ay) mice which had been reported as diabetic nephropathy model. Diabetic KK-Ay mice, diabetic KK/Ta mice and non-diabetic BALB/cA Jcl (BALB/cA) mice were studied. We analyzed glomerular lesions in all mice by morphometric analysis and immunofluorescence to determine the number of podocytes. Level of urinary albumin was also measured. Glomerular enlargement and mesangial expansion were observed in KK-Ay mice. Mean number of podocytes per glomerulus (NG pod) in diabetic KK-Ay mice was significantly lower than that in non-diabetic BALB/cA mice. Mean NG pod/glomerular area (GA) per glomerulus was also significantly decreased in diabetic KK-Ay mice. The level of urinary albumin/creatinine ratio (ACR) in diabetic KK-Ay mice was significantly higher than that in non-diabetic BALB/cA mice. These data suggest that podocyte loss might induce albuminuria in KK-Ay mice. This finding confirmed our previous report that KK-Ay mice, especially in terms of histological findings, are a suitable animal model for glomerular injury in type 2 diabetic nephropathy.