Nephropathy in KK Mice and the Effects by Glibenclamide Treatment
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概要
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KK mice were treated daily with glibenclamide from 3 to 8 months of age. The dosage of this drug was 25-75 μg/day and determined to give negative urine sugar. As control animals, age matched KK mice without this drug and nondiabetic C 57 BL mice were used.<BR>These animals were sacrificed at 8 months of age. The renal tissue was studied morphologically and morphometrically, and the results for the drugtreated KK mice and control animals were compared.<BR>The mice treated with glibenclamide showed a significant decrease in glomerular size (p<0.01) and glomerular basement membrane thickness (p<0.05) compared to the KK mice without the drug, together with a tendency to decrement of the mesangial area. Moreover, there was a linear correlation between fasting blood sugar and glomerular size in the KK mice. However, these decreased morphometric values for KK mice were still larger than those in C 57 BL mice. Accordingly, the origin of renal glomerular lesions in KK mice may be suggestive not only of the diabetic states but also of other unknown factors including genetic ones.<BR>To determine the metabolic state in the renal tissue which probably leads to characteristic glomerular lesions in KK mice, <SUP>3</SUP>H-proline or <SUP>3</SUP>H-lysine was administered intraperitoneally to KK mice without glibenclamide and C 57 BL mice which were 8 months old.<BR>The kidneys were removed from these animals after 24hr and 16 days. The ratio of the radioactivity in the renal cortex, i.e. the 16 day value (cpm)/24hr value (cpm), was greater in the KK mice than the C 57 BL mice.<BR>Such a tendency was more clearly supported by results for grain counts in the glomerular tufts using the radioautographic method.<BR>It appears therefore that after the incorporation of proline or lysine in the renal cortex or glomerular tufts, these amino acids are retained longer in KK mice than in C 57 13L mice. The results thus reflect the development of the characteristic glomerulopathy in KK mice.
- 一般社団法人 日本糖尿病学会の論文
一般社団法人 日本糖尿病学会 | 論文
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