A novel assay for detection and quantification of C-mannosyl tryptophan in normal or diabetic mice

C-Mannosyl tryptophan (C-Man-Trp) is a unique molecule in that an α-mannose is connected to the indole C2 carbon atom of a Trp residue via C-glycosidic linkage. Although serum C-Man-Trp may be a novel biomarker of renal function in humans, the biological significance of C-Man-Trp has yet to be fully investigated. In this study, a novel assay system for C-Man-Trp was established using hydrophilic-interaction liquid chromatography, followed by detecting the fluorescence intensity or mass abundance of C-Man-Trp. Using this system, we systematically assessed the amount of free monomeric C-Man-Trp in different tissues of mice. The tissue level of C-Man-Trp was high, especially in the ovaries and uterus. Other organs with high levels of C-Man-Trp included the brain, spleen, lungs, bladder, and testes. The level was low in skeletal muscle. We also investigated whether the tissue level of C-Man-Trp is affected in diabetes. In KK-Ay diabetic mice, the level of urinary C-Man-Trp excretion was increased, and the tissue levels of C-Man-Trp were decreased in the liver but increased in the kidney. These results demonstrate that C-Man-Trp is differentially distributed in numerous tissues and organs in mice, and the levels are altered by disordered carbohydrate metabolism such as diabetes.