Studies of experimental diabetes caused by xanthurenic acid, an abnormal metabolite of tryptophan.

Since 1950 we have conducted a series of experiments on the diabetic symptoms in albino rats caused by the administration of xanthurenic acid (XA), an abnormal metabolite of tryptophan. Our studies have given conclusive evidence that XA is related to the development of human diabetes, a disease generally attributes to an inadequate food intake. Evidence also suggests that there is a close relationship between animal and human diabetes.Experiments have shown that XA is a substance produced in the body as a result of intake of excess of the sodium salts of fatty acid (representing fat) and tryptophan (representing animal protein).Taking into consideration the chronic nature of human diabetes, we then studied the development of chronic diabetic symptoms in rat caused by accumulative effect of XA produced in the body when vitamin B6 deficient diet or excessive fat and tryptophan diet was administered for a long period. Then the pancreatic tissue of these rats was examined histologically. A decrease of stainability, a decrease in granules, much vacuole formation, and collapse of the protoplasm were noticeable in the β-cells of the islets of Langerhans.We then examined fairly large amount of XA in the urine of many diabetic patients by the partition paper chromatographic method. These is an undeniable etiological relationship between free XA and human diabetes since a fairly large amount of XA in a free form present in the urine was invariably present in the urines of diabetic patients.Murakami, one of our co-worker, recently showed that XA formed a binding complex with insulin. We have observed XA bound with insulin in human serum. XA-insulin complex showed a new fruorescence spectrum. The hormonal activity of XA-insulin complex was markedly decreased.From these results we may suggest that experimental diabetes in the presence of XA may be induced by the following mechanism: