Measurement of Tryptophan Metabolites in Healthy Old Men and Patients of Type 2 Diabetes Mellitus (T2DM)

Tryptophan (TRP) is one of essential amino acids for protein synthesis, but it also serves as a substrate for the generation of several bioactive compounds with important physiological roles. It is known that in mammals, the majority of free TRP is degraded through the kynurenine pathway (KP) and generates many metabolites involved in inflammation, immune response, and excitatory neurotransmission. Plasma levels of tryptophan (TRP) metabolites have not been measured extensively in patients of type 2 diabetes mellitus (T2DM). 

In this paper, the authors asked male acquaintances older than 50 years to participate in the experiments. The sample sizes and ages of participants are as follows; old men (n = 20, age; 62.4 ± 9.6) and patients of T2DM (n = 20, age 67.0 ± 10.4). Fasting plasma samples of T2DM patients were obtained early morning. Metabolites analysis was performed by a liquid chromatograph tandem mass spectrometer, the LCMS-8060 quadrupole mass spectrometer combined with Nexera X2 liquid chromatograph system (Shimadzu Corporation, Kyoto, Japan). Body mass index (BMI) and TRP metabolites have been measured in healthy old men (n = 20) and patients of T2DM (n = 20). TRP metabolites were measured by using the ultrahigh speed liquid chromatography-mass spectros-copy (Shimadzu Corporation). 

The plasma levels of 5-hydroxytryptophan (5-HTRP), 5-hydroxyindoleacetic acid (5-HIAA), kynurenic acid (KNA), 3-hydroxykynurenine (3-HKN), and 3-hydroxyanthranilic acid (3-HAA) were higher in patients of T2DM than healthy old men. Since 5HTRP and 5-HIAA belong to the serotonin pathway, and KNA, 3-HKN, and 3-HAA belong to the KN pathway of TRP metabolism, these pathways were activated more in the patients of T2DM. Since plasma levels of Indole-3-acetic acid were not elevated in T2DM, that pathway was not activated more in T2DM. Serotonin levels were not increased but 5-HIAA levels were increased in the plasma of T2DM patients, which may mean that serotonin was quickly metabolized to 5-HIAA in the patients of T2DM. 

Plasma levels of tryptophan metabolites in serotonin and kynurenine pathways increased in T2DM patients. Obesity expressed by BMI may not influence tryptophan metabolism in healthy old men and T2DM patients. These results indicate that our new method of the simultaneous measurements of all the tryptophan metabolites is the powerful measure to identify factor related to endogenous stresses seen in DM.

Article by Akikazu Takada, et al, from Japan.

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