Polysaccharides from Mushroom Fruiting Bodies Improve Insulin Resistance by Inhibiting Lipid Deposition Via Autophagy Enhancement

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Insulin resistance is the main cause of type 2 diabetes. Polysaccharide is one of the main active components in mushrooms and has been reported that certain mushroom polysaccharides have beneficial effects against type 2 diabetes. However, the structural features and mechanisms of polysaccharides with hypoglycemic activity have not been elucidated. In this paper, six alkali-soluble total polysaccharides, six neutral polysaccharides and six acidic polysaccharides were extracted and purified from mushrooms fruiting bodies of different species. The effects of these polysaccharides on improving insulin resistance were compared using high fatty acids and glucose-induced hepatocytes. Among them, the neutral polysaccharide AAMP-N of Armillaria mellea fruiting body showed the most significant activity, suggesting that galactoglucan is the main active domain. AAMP-N inhibited intracellular fat accumulation and enhanced insulin sensitivity by activating autophagy. Autophagy is an essential lysosomal degradation pathway implicated in the development of type 2 diabetes. Consistent with the in vitro results, AAMP-N enhanced hepatic autophagy, lowered blood glucose, and modulated lipid metabolism in db/db mice. In addition, AAMP-N also protected damaged pancreatic islets in mice. Our results demonstrated for the first time a role of natural polysaccharides from mushrooms in the improvement of insulin sensitivity and metabolism, and provided basis for the development of mushroom polysaccharides as hypoglycemic healthy food. Funding Statement: This work was supported by National Natural Science Foundation of China (No. 31872674), Jilin Province Pharmaceutical Industry Development Fund (No. 20180311068YY), Jilin Province Development and Reform Commission (2018C047-2), and Fundamental Research Funds for the Central Universities (No. 2412017FZ018). Declaration of Interests: The authors have declared no conflicts of interest. Ethics Approval Statement: All experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals of Northeast Normal University.