Hexosamine Metabolism and Diabetes Mellitus

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With regard to pathogenesis of diabetic angiopathy, hexosamine has roused a particular interest from the fact that it is an important component of glycoproteins and mucopolysaccharides which play a role in vascular lesions. Recently we found that the level of bound hexosamine in urine in untreated diabetic patients is decreased remarkably when blood sugar is controlled by insulin, which indicates that urinary excretion of bound hexosamine is well correlated with severity of diabetes. An attempt was made in the present study to clarify the carbohydrate metabolism, insulin secretion and retinal findings in hexosamine-treated rats in comparison with streptozotocin-induced diabetic rats. 1) Male Splague-Dawley rats were individually maintained in metabolic cages on chow and water ad libitum. They were made to fast overnight and injected intravenously with 65mg/kg body weight of streptozotocin. Twenty-four hour urine specimens were collected in 0.1 % sodium azide. Urinary volume and sugar increased rapidly as severe diabetes was established. Twenty-four hour urinary bound hexosamine also increased markedly. There was a slight but significant rise in liver hexosamine content in the diabetic rats, 2 months after the injection. 2) Glucosamine (250mg/kg body weight) was injected intraperitoneally daily to normal rats for 2 months. There was a significant elevation of urinary bound hexosamine in the glucosamine treated rats, though the rate of increase was less than in diabetic rats. Oral glucose tolerance tests were performed with gastric tubing. No significant differences were observed in serum glucose levels between the normal and treated rats, except at the 3rd hour when glucose was still somewhat elevated in the latters. There was no insulin response to administration of glucose in the glucosamine treated rats, although there was no significant change at the fasting level of insulin between the two groups. No significant decrease in glucokinase activity was observed in the treated rats in comparison with a marked decrease in diabetic rats. G 6 Pase activity increased significantly in both diabetic rats and glucosamine treated ones, though the amount of the increase was much smaller in the latter group. 3) No remarkable histological changes appeared in the liver and kidney in both diabetic rats and glucosamine treated ones compaired to normal ones. The latter showed as significant increase in urinary protein excretion as the diabetic rats. No remarkable diabetic changes such as microaneurysm were detected in the retinal capillaries of either the diabetic rats or the glucosamine treated ones. It was observed that the ratio of endothelial cells to the mural cells of the retinal capillaries increased. These data suggest that glucosamine is at least partially responsible for microangiopathy. 4) Liver hexosamine content and excretion of urinary bound hexosamine increased in the diabetic rats, but no significant changes were observed in the glucosamine synthetase activity of liver which is the main site of glucosamine biosynthesis. A prolonged administration of glucosamine increased tissue and urinary bound hexosamine as in the diabetic state. 10 μpCi of U-14C-glucose and 15μCi of U-14C-pyruvate were injected into normal and diabetic rats. Incorporation of 14C-glucose into urinary bound glucosamine decreased in the diabetic rats as compared with the normal in the first 24 hours urine specimen, but when dilution with high blood sugar in the diabetic rats was taken into consideration, the incorporation was not impaired but increased. Incorporation of U-14C-pyruvate into urinary glucosamine inclined to increase in the diabetic rats. Therefore, the increase in hexosamine in the diabetic specimen is most likely due to increased biosynthesis of hexosamine, from glucose and through gluconeogenesis.
Japan Society of Clinical Chemistryの論文

Hexosamine Metabolism and Diabetes Mellitus

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