Examination of the Pathogenesis of Diabetic Nephropathy in OLETF Rats.

Abstract

ABSTRACT. We conducted protein loading to examine the progression and pathogenesis of diabetic nephropathy. For this experiment, male OLETF, LETO, F344 and BN rats were used. This experiment was performed on rats between 5 and 30 weeks of age. Examination parameters included body weight, food intake, oral glucose tolerance test (OGTT), urinary protein level (UP), urinary albumin level (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 control group, GFR were higher than those in other strains. Glomerular hypertrophy and kidney weights were markedly increased in protein-loaded groups in OLETF rats. Thirty weeks after birth, EM showed that the number of polyethyleneimine (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 proteinloaded group than those in the control group. LM showed that the number of exudative lesions with fibrin-cap in the protein-loaded OLETF group was significantly increased than those in control group. In OLETF rats, protein loading caused deterioration of nephropathy at 30 weeks of age. Therefore, it was demonstrated that not only blood sugar control but also protein intake factors play important roles in the deterioration of nephropathy in OLETF rats.-KEY WORDS: diabetes, nephropathy, OLETF, protein, rat.J. Vet. Med. Sci. 61(11): 1219-1228, 1999 nephropathy did not differ from that in untreated OLETF rats [8,9]. As a factor in this finding, food intake and protein intakes were decreased because sucrose-loaded rats liked to ingest sucrose. The decrease in protein intake may have influenced deterioration of nephropathy. Furthermore, in humans, it has been reported that a protein-restricted diet is effective in treating diabetic nephropathy. Therefore, we speculated that there might be an association between deterioration of diabetic nephropathy and protein intake. In this study, we performed protein loading in OLETF rats, and examined the involvement of protein in deterioration of diabetic nephropathy. MATERIALS AND METHODS Establishment of experimental groupsWe used male OLETF and LETO rats bred at the Tokushima Research Institute of Otsuka Pharmaceutical Co., Ltd. as well as F344 and BN rats purchased from Charles River Japan Inc. (Yokohama). In all strains, we established control groups in which standard chow (CRF-1; Oriental Yeast Co., Ltd., containing 23% crude protein) was given and 40% protein-loaded groups (40% crude protein was contained in food). The food composition was shown in Table 1. Eight animals were assigned to each group. This experiment was conducted in rats between 5 and 30 weeks of age. Animals were acclimated in the specific pathogenfree (SPF) room under the following conditions; temperature, 23 ± 2°C; humidity, 60 ± 10%; and lighting cycle, 12 hr (7:00 a.m. to 7:00 ...

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