Production of L-tryptophan-derived catabolites in hepatocytes from streptozotocin-induced diabetic rats

Recently the L-tryptophan (Trp) metabolites such as L-kynurenine(Kyn), L-kinurenic acid, quinolinic acid (QA) and picolinic acid (PA) have been shown physiologically important in central nervous and immune system, and various enzyme activities concerning their production were reported to be affected by insulin-dependent diabetes mellitus. However, the states of these metabolites in diabetes have not been clarified enough yet.

The present study was performed to make clear the states of the productions of L-Kyn, QA, PA and nicotinamide (Nam) in vitro in the hepatocytes prepared from streptozotocin (STZ)-induced diabetic rats using [5-3H]L-Trp.

The diabetic model rats were made by STZ injection (60 mg/kg) and the hepatocytes isolated from the rats were incubated with [5-3H]L-Trp. The amounts of metabolites derived from L-Trp were determined by the isotope-dilution methods.

The alpha-amino-beta-carboxymuconate-epsilon-semiarldehyde decarboxylase (ACMSD) mRNA level in the diabetic group was greatly higher than that in the control group. In the STZ-induced diabetes group, the amount of [5-3H]L-Trp converted to tritiated water, L-Kyn or QA were found to be more than 3 times of that in the control group, respectively. The produced amounts of PA and Nam were not significantly different between the diabetic and the control groups.

It is suggested that STZ-diabetes mellitus causes augmentations of both L-Kyn and QA generations but not those of PA and Nam in liver, indicating the possibility that the immune and neuronal systems of insulin dependent diabetes mellitus would be influenced by the increased amounts of LKyn and QA but not by those of PA and Nam.