Diabetes and Tryptophan Metabolism

Abstract

Tryptophan, an essential amino acid, can be metabolized to several kinds of physiologically active metabolites. Accumulating data indicate that an altered metabolism of tryptophan and its active metabolites have important roles for the pathogenesis and development of complications of diabetes mellitus. Changes in tryptophan-kynurenine and tryptophan-methoxyindole pathways are related to several pathophysiological mechanisms of type 1 or type 2 diabetes. Particularly, serotonin, melatonin, and their receptors would be novel targets not only to better understand the pathogenesis of diabetes but also to develop new antidiabetic agents. Keywords IntroductionIn addition to the traditional knowledge, recent studies show that amino acids are also among the regulators of the phosphorylation cascade of proteins and expression of genes. Moreover, they are crucial precursors of hormones and nitrogenous substances with outstanding biological importance. Even though physiological concentrations of amino acids and their metabolites are necessary for physiological processes, their elevated levels might be pathogenic in several disorders. Several

Serum Amino Acids in Association with Prevalent and Incident Type 2 Diabetes in A Chinese Population

“…Tryptophan can be metabolized to several kinds of physiologically active metabolites such as kynurenine, kynurenic acid, and serotonin via two metabolic pathways: tryptophan–kynurenine and tryptophan–methoxyindole. The changes in the two pathways have been related to several pathophysiological mechanisms of type 2 diabetes [23].…”

Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case–Cohort Study

“…IDO1, a rate-limiting enzyme for the conversion of tryptophan to kynurenine, is upregulated in response to inflammatory cytokines (29) and may act as a local compensatory mechanism to limit obesity-induced inflammation (30). Thus, in inflammatory states such as obesity, the tryptophan–kynurenine pathway may shift in favor of breakdown of tryptophan into downstream products (31, 32). This hypothesis is supported by our finding that the baseline Kyn/Trp ratio was positively associated with insulin resistance but that 1-year changes in the same ratio was inversely associated with insulin resistance.…”

Indigenous Subarctic Food Systems in Transition: Amino Acid Composition (Including Tryptophan) in Wild-Harvested and Processed Meats

“…Second, the amount of dietary Trp destined for central 5-HT is also limited. Only a small portion of Trp consumed is metabolized via the methoxyindole pathway for 5-HT synthesis due to competition with the more dominant kynurenine pathway, as well as protein synthesis, and alternative metabolites such as melatonin and tryptamine [10, 46, 47]. Most of this 5-HT pool is synthesized in the gut, reserving a small and controlled amount for the CNS [10, 48].…”

“…Yet central 5-HT stores cannot be inferred from dietary Trp and LNAA content alone. Trp availability and transport for central 5-HT is also dictated by other factors: health conditions or medications causing Trp malabsorption [46]; excess Trp oxidation or metabolism [47, 49–51] changes in the kynurenine pathway [47, 52]; changes in peripheral 5-HT production [52, 53]; changes in gut microbiota [53]; chronic inflammation [54, 55]; and prolonged stress [51, 56, 57].…”