REGULATION OF TRYPTOPHAN-NIACIN METABOLISM IN DIABETIC RATS

The regulation of tryptophan-niacin metabolism was studied in vivo with regard to the activity of liver α-amino-β carboxymuconate-ε-semialdehyde decarboxylase (picolinic carboxylase) using non-diabetic and diabetic rats. Non-diabetic rats and rats with diabetes induced by alloxan were fed on a commercial diet for 80 days, followed by a niacin-free experimental diet for the next 16 days. Protamine zinc insulin (5 units/head) was injected into 3 diabetic rats every 12 hr from the 10th to 16th day of the start of administration of the experimental diet. At the 14th day of the experimental diet, 24-hr urine was collected and urine collection repeated after the oral administration of L-tryptophan (100mg/rat). At the end of the metabolic experiments, the content of total nicotinate in liver was determined and the enzyme activity of liver picolinic carboxylase was assayed. The urine was analyzed for N-methylnicotinamide (MNA). The amount of urinary excreted MNA per diet or per administered tryptophan was significantly reduced in diabetes, and insulin treatment rather lessened the amount in spite of normal blood glucose levels. Although the activities of liver picolinic carboxylase in diabetic and insulin-treated diabetic rat groups were higher than that of non-diabetic groups, no difference was observed between the former two groups. As the content of total nicotinate in liver was found to be almost constant among these three groups, the reduction of the urinary MNA in the insulin-treated group is considered to be attributable to the elevated retention of nicotinate that is associated with the increased weight gain. The activity of liver picolinic carboxylase was found to be inversely proportional to the amount of urinary excreted MNA and appeared to be roughly proportional to the ratio, of the amount of L-tryptophan administered to the urinary MNA. Thus, the amount of tryptophan required to produce a constant amount of MNA is expected to increase proportionally according to the elevation of the activity of liver picolinic carboxylase.