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 mellit us, a genetically obese rat strain, Wistar fatty. These rats show obes ity-related features such as hyperinsulinemia and hyperlipemia, and on ly males develop diabetic features including hyperglycemia, glucoseuri a and polyuria as they age. Histopathological study demonstrated a dep osition of PAS-positive granules in the epithelial cells and a diffuse thickening of the mesangial area and moderate changes of the renal tu bules. We found that ICAM-1 is expressed on the glomeruli of male Wist ar fatty rats and the expression is associated with the development of nephropathy; it is weak at 5 weeks, becomes markedly strong at 15 wee ks and progresses further at 29 weeks of age, We tried in vivo adminis tration of monoclonal antibody, anti-ICAM-1 alone or together with ant i-LFA-l into male Wistar fatty rats during the period from 5 weeks to 17 weeks of age, The treatment, however, could not prevent the develop ment of nephropathy, ICAM-1 expressed on the glomeruli of Wistar fatty rats seems not to play a key role in development of the nephropathy b y mediating leukocyte infiltration. It will be a useful marker of the development of the disease.