Quantification of serum C-mannosyl tryptophan by novel assay to evaluate renal function and vascular complications in patients with type 2 diabetes

Abstract

C-Mannosyl tryptophan (CMW) is a unique glycosylated amino acid, and a candidate novel biomarker of renal function. In type 2 diabetes (T2D), a combination of metabolites including CMW has recently been the focus of novel biomarkers for the evaluation of renal function and prediction of its decline. However, previous quantification methods for serum CMW have several limitations. We recently established a novel assay for quantifying serum CMW. Serum CMW from 99 Japanese patients with T2D was quantified by this assay using hydrophilic interaction liquid chromatography. The serum CMW levels were cross-sectionally characterized in relation to clinical features, including renal function and vascular complications. Serum CMW level was more strongly correlated with serum creatinine and cystatin C levels and with eGFR than with albumin urea level. The ROC curve to detect eGFR < 60 ml/min/1.73 m2 revealed that the cutoff serum CMW level was 337.5 nM (AUC 0.883). Serum CMW levels were higher in patients with a history of macroangiopathy than in those without history. They correlated with ankle-brachial pressure index, whereas cystatin C did not. Serum CMW levels quantified by the novel assay could be useful in evaluation of glomerular filtration of renal function and peripheral arterial disease in T2D.

Neopetrosins A–D and Haliclorensin D, Indole-C-Mannopyranosides and a Diamine Alkaloid Isolated from the South China Sea Marine Sponge Neopetrosia chaliniformis

“…The 1 H NMR spectrum exhibited signals of an exchangeable proton (δ H 12.4, s), four protons attached to an aromatic moiety (δ H 7.20, 1H, m; δ H 7.21, 1H, m; δ H 7.48 and 7.82, d, J = 7.1), and protons of a sugar moiety (Table 1). The 13 C NMR spectrum showed nine sp 2 hybridized carbon signals (one ester carbon at δ C 162.6, four sp 2 tertiary hybridized carbons at δ C 112.7, 119.4, 121.9 and 122.8, four sp 2 quaternary hybridized carbons at δ C 100.0, 125.0, 136.9, and 147.2), and six sugar carbons (δ C 58.6, 60.5, 67.9, 69.5, 77.9, and 81.2) (Table 2). Heteronuclear multiple bond correlations (HMBCs) observed from NH-1 to C-2/C-3/C-4a/C-7a, from H-4 to C-3, and from H-7 to C-4a, together with the 1 H− 1 H correlated spectroscopy (COSY) correlation of H-4/H-5/H-6/H-7, confirmed the presence of an indole moiety.…”

“…C -Mannosyl tryptophan ( 5 ) was initially discovered in RNase2 from human urine and erythrocytes. , It was also found in marine ascidians and sponges and can be used as a promising biomarker candidate of renal function . Related compounds with potent cytotoxicities were reported from Radix isatidis , a traditional Chinese medicine Ban Lan Gen …”

“…11 C-Mannosyl tryptophan is a degradation product of autophagy in cultured cells 12 and can be used as a promising biomarker candidate of renal function. 13 Related compounds with potent cytotoxicities were reported from Radix isatidis, a traditional Chinese medicine Ban Lan Gen. 14 In our search for bioactive compounds from marine sponges, four new unusual indole C-glycoside alkaloids, neopetrosins A−D (1−4), together with one new diamine alkaloid, haliclorensin D (6), and two known analogues, C-mannosyl tryptophan (5) 10 and haliclorensin B (7), 15 were isolated from the marine sponge Neopetrosia chaliniformis collected off Xisha Island in the South China Sea. The planar structures and absolute configurations of 1−6 were determined by the spectroscopic analysis, single-crystal X-ray diffraction, calculated ECD, and DP4+ probability analyses.…”

Protein C-Mannosylation and C-Mannosyl Tryptophan in Chemical Biology and Medicine

“…Recently, it was reported that higher urine C -Man-Trp levels were associated with a higher risk of adverse kidney events, such as kidney failure and acute kidney injury, and death [ 136 ]. We examined the level of serum C -Man-Trp in patients with type 2 diabetes, and found that the level of serum C -Man-Trp is significantly correlated with that of the creatinine or cystatin C, indicating that serum C -Man-Trp is useful to estimate the renal function in patients with type 2 diabetes [ 137 ]. It is also noteworthy that the level of serum glucose showed no correlation with that of serum C -Man-Trp of diabetic patients whose renal function is maintained (eGFR > 60 mL/min/1.73 m 2 ).…”

“…In type 2 diabetic patients, the level of serum C -Man-Trp was increased with the progression of peripheral artery disease as assessed by ankle-brachial pressure index (ABI) [ 137 ]. This may be compatible with the fact that C -mannosylated TSP-1 was upregulated in aortic tissues of diabetic Zucker fatty rats [ 124 ].…”