Expression of ICAM-1 on glomeruli is associated with progression of diabetic nephropathy in a genetically obese diabetic rat, Wistar fatty.
We developed an animal model for non-insulin-dependent diabetes mellitus, a genetically obese rat strain, Wistar fatty. These rats show obesity-related features such as hyperinsulinemia and hyperlipemia, and only males develop diabetic features including hyperglycemia, glucoseuria and polyuria as they age. Histopathological study demonstrated a deposition of PAS-positive granules in the epithelial cells and a diffuse thickening of the mesangial area and moderate changes of the renal tubules. We found that ICAM-1 is expressed on the glomeruli of male Wistar fatty rats and the expression is associated with the development of nephropathy; it is weak at 5 weeks, becomes markedly strong at 15 weeks and progresses further at 29 weeks of age. We tried in vivo administration of monoclonal antibody, anti-ICAM-1 alone or together with anti-LFA-1 into male Wistar fatty rats during the period from 5 weeks to 17 weeks of age. The treatment, however, could not prevent the development of nephropathy. ICAM-1 expressed on the glomeruli of Wistar fatty rats seems not to play a key role in development of the nephropathy by mediating leukocyte infiltration. It will be a useful marker of the development of the disease.
Matsui
H
H
Discovery Research Laboratories II, Takeda Chemical Industries Ltd., Ibaraki, Japan.
Suzuki
M
M
Tsukuda
R
R
Iida
K
K
Miyasaka
M
M
Ikeda
H
H
D000375:Aging; D000419:Albuminuria; D000818:Animals; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology*; D005920:Glomerular Mesangium / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis*; D007678:Kidney Glomerulus / Q000473:pathology* / Q000503:physiopathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D009765:Obesity / Q000235:genetics*; D011507:Proteinuria; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012727:Sex Characteristics
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1