Diabetes tryptophan metabolism

Urine Progressive form of albuminuria from the nonprogressive form of albuminuria Type 1 diabetic patients normoalbuminuric56. After 5.5 years micro/macroalbuminuric 26 normoalbuminuric 26 GC-MS LC-MS Acylcarnitines, acyl-glycines, and metabolites related to the tryptophan metabolism (56)... 

Salter M and Pogson Cl (1985) The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes. Biochemical Journal 229,499-504. 

It has been observed (D6) Aat addition of vitamin Be to insulin therapy allowed the employment of lower doses of insuhn and, in one subject, the total cessation of insulin administration. Finally, Oka and Leppanen (04) studied the tryptophan metabolism in 10 patients with diabetes mellitus and in 12 control subjects by determining the urinary excretion of 5-hydroxyindoleacetic acid, kynurfenine, and anthranilic, 3-hydroxyanthranilic, and xanthurenic acids before and after a load of 2 g L-tryptophan. The authors noted a markedly increased excretion of... 

Pla. Pelikw, V., Novosadov4, J., and Kaldb, M., Changes in tryptophan metabolism in diabetic patients. Vnitmi Lekar. 8, 668-673 (1962). 

In view of the hypoglycemic and insulinase-inhibitory action of l-tryptophan, it seemed pertinent to Mirsky to study the effect of various metabolic products of tryptophan on the blood sugar of normal and diabetic rats (M9), A statistically significant hypoglycemic response was produced after oral administration of anthranilic acid, niacin, indole-3-acetic acid, 5-hydroxytryptophan, and serotonin. A hypoglycemic fol-... 

From such a complex of data one can draw conclusions which permit us to either accept or reject the evidence for a direct connection of tryptophan and its metabolism with diabetes. Further investigations are therefore necessary. 

In subsequent studies (K7), 9 members of 3 different families were loaded with 10 g OL-tryptophan which resulted in a 10-20-fold increase in the 24-hour urinary excretion of kynurenine, 3-hydroxykynurenine, and xanthurenic acid. It appears to be a genetically conditioned disturbance, with dominant inheritance, involving metabolic reactions dependent upon pyridoxine. In most subjects the urinary changes after tryptophan loading could be corrected by vitamin Be therapy. The following diseases were found in this order of frequency in these subjects and their families bronchial asthma, chronic urticaria, anemia, diabetes, arices, and crural ulcers. Knapp s (K7) conclusion is that these disorders may be partially attributable to metabolic disturbances. 

A calorie intake of 1,800-2,500 kcal/day (ca. 30 kcal/ kg BW/day) is guaranteed by the adequate administration of fats (70-140 g) and carbohydrates (280-325 g). Consideration should be given to the fact that cirrhotic patients show a resistance to insulin and a glucose intolerance, with a tendency to develop a diabetic metabolic condition. For this reason, it might well be necessary to administer insulin. Carbohydrates reduce the plasma levels of ammonia and free tryptophan. 

The increased plasma kynuremne pool and the induced xanthurenic acid urinary excretion have several implications in the assessment of diazinon noncholinergic toxicity. An increase in xanthurenic acid formation may alter glucose metabolism. Xanthurenic acid has been reported to form a complex with insulin and damage pancreatic P cells. Elevated plasma kynurenin may alter kynurenin transport into the brain. Since more than 40% of brain kynurenin originates from the systemic circulation, cerebral biosynthesis of neuroactive kynurenin metabolites such as quinolinic acid and kynurenic acid may change. Finally, the availability of L-iryptophan for other L-lryptophan-dependent processes may be reduced. Tryptophan is the metabolic precursor for. serotonin and nicotinic adenine dinucleotidc. Diabetes, bladder cancer, and neurological disorders may be the toxic consequences of diazinon-altered L-tryptophan metaboli.sm (Seifert and Pewnim, 1992 Pewnim and Seifert, 1993). 

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