Diabetic Microangiopathy and Metabolism of Glycosides

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It is uncertain whether the marked deposition of glycoproteins in lesions of small vessels in diabetics is related to increased synthesis or decreased breakdown of materials. Glucosamine is an important component of glycoprotein and we demonstrated that liver glutamine-fructose-6-paminotransferase, a key enzyme in the synthesis of glucosamine is not significantly changed in diabetic rats. As glycosidases in lysosomes have been suggested to participate in the catabolism of glycoprotein, changes in the activities of glycosidases, β-N-acetylglucosaminidase, fβ-glucuronidase, β-galactosidase and β-glucosidase were measured in the intestine, liver, lddney, spleen and serum of the streptozotocin diabetic rats. The activities of the first three enzymes listed above were found to be much reduced in the kidney in spite of pronounced increase in their serum activities. The kidney is one of the main sites of vascular lesions in diabetes. Our data suggest that the decreased activities of lysosome glycosidases in the kidney may be related to accumulation of glycoprotein and so to the pathogenesis of diabetic vascular lesions. Cathepsin D showed no significant change in activity in either liver or kidney in diabetic rats. β-N-acetylglucosaminidase activity was significantly decreased 4 weeks after streptozotocin injection. On the contrary, its activity in the serum was greatly increased 4 and 8 weeks after the injection. β-Glucuronidase and β-galactosidase activities showed similar changes. Subcutaneous injection of 4 U Lente insulin once daily for two days resulted in increase in β-N-acetylglucosaminidase activity in the kidney and decrease in the serum. The changes in the serum and kidney enzyme levels were reciprocal. To exmine these changes, the isozymes of β-N-acetylglucosaminidase of rats were examined by DEAE-cellulose column chromatography, and at least 3 major isozymes were found in both the kidney and liver. The main isozyme was type II in normal rat kidney and type III in normal rat liver. The activity of the type II isozyme in the kidney was markedly lowered when the total activity was decreased in diabetes and its normal activity was restored in insulin treatment in parallel with increase in the total activity in diabetes. No singificant changes were found in the chromatographic pattern of isozymes in the liver in diabetes. It was also investigated whether there is any available materials, possesing the same characteristics of β-N-acetylglucosaminidase activity as kidney. Rat retina and human tear β-N-acetylglucosaminidase were shown decreased in the diabetic stage and to have a similar isozyme pattern. In human subjects, the serum activities of β-N-acetylglucosamidase were found to be significantly increased in diabetic patients and the increase was greater in patients with retinopathy and in poorly controlled patients than in patients without retinopathy and in well controlled patients. The diabetic patients were followed up with occasional examinations of optic fundi and measure-ments of serum enzyme activity. Data suggested that the patients with retinopathy showed high activities and when the activity was kept lowered for a few months, retinopathy, if any, showed an improvement. Thus, the decreased activities of β-glycosidases in the diabetic kidney and retina may be one of the factors responsible for the pathogenisis of microangiopathy and reciplocal increase in serum activities may be an index for the development of microangiopathy.
Japan Society of Clinical Chemistryの論文

Diabetic Microangiopathy and Metabolism of Glycosides

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