Abstract
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.
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.
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.
To determine the metabolic state in the renal tissue which probably leads to characteristic glomerular lesions in KK mice, 3H-proline or 3H-lysine was administered intraperitoneally to KK mice without glibenclamide and C 57 BL mice which were 8 months old.
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.
Such a tendency was more clearly supported by results for grain counts in the glomerular tufts using the radioautographic method.
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.
