Diabetic microangiopathy in KK mice

Autor: Rafael A. Camerini-Davalos, M. Chen, A.S. Reddi, Werner Oppermann
Rok vydání: 1978
Předmět:
Zdroj: Experimental and Molecular Pathology. 29:442-447
ISSN: 0014-4800
DOI: 10.1016/0014-4800(78)90084-9
Popis: KK mice with genetic diabetic glomerulosclerosis were treated with 250 mg/kg of pyridinolcarbamate (PDC), an antibradykinin agent, by 20 days of age and the kidney glucosyltransferase activity was measured. This enzyme facilitates the attachment of glucose to hydroxylysine-galactose unit of the basement membrane, which is glycoprotein in nature. No effect of PDC on the glucosyltransferase activity was observed up to 50 days of treatment. However, after 80 days of treatment, the enzyme activity was significantly increased. This finding was associated with a similar increase in total protein synthesis by the renal cortex of the treated KK mice. Amelioration of severity to only mild glomerulosclerosis was observed after 50 days of PDC administration. However, after 80 days of drug treatment, no severe type of glomerulosclerosis was present. PDC had no effect on either the fasting blood sugars or serum immunoreactive insulin levels. However, the oral glucose tolerance appeared to be improved in mice treated for 80 days. Glycogen synthesis by diaphragm muscle and total lipid synthesis by epididymal fat pad were significantly increased after 80 days of drug treatment, indicating increased tissue sensitivity to endogenous insulin. The observation that glucosyltransferase activity responded to PDC treatment with concomitant prevention of diabetic glomerulosclerosis suggests a relationship between this enzyme activity and glycoprotein synthesis in the kidney. It is suggested that PDC is a potential drug for the treatment of diabetic glomerulosclerosis.
Databáze: OpenAIRE