Diabetic microangiopathy in KK mice: IV. Effect of pyridinolcarbamate on kidney glucosyltransferase activity and glomerulosclerosis

Abstract

KK mice with genetic diabetic glomerulosclerosis were treated either with saline or 250 mg/kg of pyridinolcarbamate (PDC), an anti-atherosclerotic agent, from 2 months of age. Both groups of mice were sacrificed at 4 and 6 months of age and their kidneys were used for the determination of glucosyltransferase activity and for light microscopic studies. No effect of PDC on enzyme activity was found in mice treated for 2 months (age of mice was 4 months). However, in mice treated with PDC for 4 months (age of mice was 6 months), the glucosyltransferase activity was significantly increased. PDC delayed the progression of glomerulosclerosis from mild to the severe form after 2 and 4 months of treatment, resulting in only 31 and 16% of mild glomerulosclerosis, respectively. The data suggest that chronic treatment of PDC delays or even prevents the progression of the severe form of genetic diabetic glomerulosclerosis in KK mice. The differential response of glucosyltransferase activity to PDC treatment in KK mice with varying degrees of glomerulosclerosis suggests a relationship between this enzyme activity and glycoprotein synthesis in kidneys of these mice.