重要食药用菌多糖降血糖分子机制研究进展

Hypoglycemic effect of important edible and medicinal fungi polysaccharides: a review

摘要:

目前以糖尿病为代表的糖代谢紊乱疾病愈演愈烈，严重危害人体健康。食药用菌多糖因其具有良好的调节糖代谢作用而被关注，但其调节糖代谢的作用机制并未被很好地综述。本文从关键基因、蛋白、信号通路等方面综述了食药用菌活性多糖的降血糖机制，包括抑制蛋白酪氨酸磷酸酶1B (protein tyrosine phosphatase-1B，PTP-1B)、调节胰岛素信号通路、促进糖代谢和抑制糖异生、抗氧化和抗炎、调节肠道菌群等。然而，糖代谢紊乱不只是关键基因突变或靶点功能异常所致，而是整体代谢的多重异常共同导致的结果。代谢组学因其可以反映整体代谢变化的独特优势成为探究食药用菌多糖降糖机制的新型手段。采用代谢组学，研究人员发现食药用菌多糖通过调节氨基酸代谢改善糖异生和胰岛素抵抗，通过调节脂肪酸代谢缓解细胞脂毒性和氧化应激并对抗炎症，通过调节胆汁酸代谢维持血脂平衡和调节肠道菌群以及通过调节核苷酸代谢改善肾脏病变。若能将整体调控机制与关键位点结合探究，将加快多糖类新药开发的脚步。

Abstract:

Currently, the prevalence of disorders of glucose metabolism is soaring seriously, especially diabetes. Polysaccharides of edible and medicinal fungi are focused since they exhibit significant benefits against diabetes. However, the mechanisms of them against diabetes are not reviewed well. In this paper, we reviewed the hypoglycemic mechanisms of polysaccharides of edible and medicinal fungi against glucose disorders, taking protein tyrosine phosphatase-1B (PTP-1B) inhibition, insulin pathway regulation, glucose metabolism promotion and gluconeogenesis inhibition, anti-oxidation and anti-inflammation and regulation of intestinal microbiota as examples. However, glucose disorders were not only due to the mutations of key genes or the dysfunctions of key targets, but also caused by multiple abnormalities in overall metabolism. Thus, metabolomics emerged as a new tool for unveiling the mechanisms of polysaccharides of edible and medicinal fungi, since its priorities of probing the systematic changes. Based on it, it was found that polysaccharides of edible and medicinal fungi may ameliorate gluconeogenesis and insulin resistance by modulating amino acid metabolism, relieve cytotoxicity, oxidative stress and inflammation by regulating fatty acid metabolism, maintain serum glucose and microbiota homeostasis by regulating bile acids and ameliorate nephropathy in diabetes by modulating nucleotide metabolism. Combining the considerations of overall mechanisms and key targets may benefit the drug developing of polysaccharides against glucose disorders.