Mannose is a glucose-associated serum metabolite mainly released by the liver. Recent studies have shown several unexpected pleiotropic effects of mannose including increased regulatory T cells (Tregs), prevention of auto-immune disease and ability to reduce growth of human cancer cells. We have previously shown in large cohorts that elevated serum mannose levels are associated with future development of type 2 diabetes (T2D) and cardiovascular disease. However, potential direct effects of mannose on insulin sensitivity in vivo or in vitro are unknown. We here show that administration of mannose (0.1 g/kg BW twice daily) for one week in man did not elicit negative effects on meal-modified glucose tolerance, markers of inflammation or insulin levels. Tregs number and insulin signaling in human liver cells were unchanged. These data suggest that mannose is a marker, and not a mediator, of insulin resistance. To verify this, we examined serum mannose levels during long-term euglycemic hyperinsulinemic clamps in non-diabetic and T2D individuals. Mannose was reduced by insulin infusion in proportion to whole-body insulin sensitivity. Thus, mannose is a biomarker of insulin resistance which may be useful for the early identification of diabetic individuals with insulin resistance and increased risk of its complications.

中文翻译：

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甘露糖是一种胰岛素调节的代谢产物，反映了人体对全身胰岛素的敏感性。

甘露糖是主要由肝脏释放的葡萄糖相关的血清代谢物。最近的研究表明，甘露糖具有多种出乎意料的多效性作用，包括增加调节性T细胞（Tregs），预防自身免疫性疾病以及减少人类癌细胞生长的能力。我们先前在大型队列研究中显示，血清甘露糖水平升高与2型糖尿病（T2D）和心血管疾病的未来发展有关。然而，甘露糖在体内或体外对胰岛素敏感性的潜在直接作用尚不清楚。我们在这里显示，在男性中施用甘露糖（每天两次，每次0.1 g / kg体重）一周不会对餐后修改的葡萄糖耐量，炎症标志物或胰岛素水平产生负面影响。人肝细胞中的Treg数和胰岛素信号均未改变。这些数据表明，甘露糖是胰岛素抵抗的标志物而不是介体。为了证实这一点，我们在非糖尿病和T2D患者中进行了长期正常血糖高胰岛素钳制期间检查了血清甘露糖水平。胰岛素输注与全身胰岛素敏感性成比例地减少了甘露糖。因此，甘露糖是胰岛素抵抗的生物标志物，其可用于早期鉴定具有胰岛素抵抗并增加其并发症风险的糖尿病个体。