Examination of the pathogenesis of diabetic nephropathy in OLETF rats

We conducted protein loading to examine the progression and pathogenesis of diabetic nephropathy. For this experiment, male OLETF, LETO, F344 and BN r ats were used. This experiment was performed on rats between 5 and 30 weeks of age. Examination parameters included body weight, food intake, oral glu cose tolerance test (OGTT), urinary protein level (UP), urinary albumin lev el (UA), glomerular filtration rate (GFR), kidney weights, light microscopy (LM) and electron microscopy (EM). in the protein-loaded OLETF group, the UP level was markedly increased 20 weeks or more after birth. In OLETF cont rol group, GFR were higher than those in other strains. Glomerular hypertro phy and kidney weights were markedly increased in protein-loaded groups in OLETF rats. Thirty weeks after birth, EM showed that the number of polyethy leneimine (PEI) of the glomerular basement membrane (GBM) in protein-loaded OLETF group was significantly decreased compared to that in control group. These changes in OLETF rats were more marked in the protein-loaded group t han those in the control group. LM showed that the number of exudative lesi ons with fibrin-cap in the protein-loaded OLETF group was significantly inc reased than those in control group. In OLETF rats, protein loading caused d eterioration of nephropathy at 30 weeks of age. Therefore, it was demonstra ted that not only blood sugar control but also protein intake factors play important roles in the deterioration of nephropathy in OLETF rats.