PMID- 34865748 OWN - NLM STAT- MEDLINE DCOM- 20211208 LR - 20211214 IS - 1873-7145 (Electronic) IS - 0963-9969 (Linking) VI - 150 IP - Pt A DP - 2021 Dec TI - Coix seed polysaccharides alleviate type 2 diabetes mellitus via gut microbiota-derived short-chain fatty acids activation of IGF1/PI3K/AKT signaling. PG - 110717 LID - S0963-9969(21)00616-5 [pii] LID - 10.1016/j.foodres.2021.110717 [doi] AB - Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years. Coix seed (CS) as a homologous substance of traditional Chinese medicine and food, its polysaccharides can improve the symptoms of patients with metabolic disorders. Since most plant polysaccharides are difficult to digest and absorb, we hypothesized that Coix seed polysaccharides (CSP) exert hypoglycemic effects through the gut. In this study, the underlying mechanisms regulating hypoglycemic effects of CSP on a T2DM mouse model were investigated. After treatment with CSP, serum insulin and high-density lipoprotein cholesterol levels were increased, while total cholesterol, triglycerides and low-density lipoprotein cholesterol levels were decreased in T2DM mice. In addition, CSP treatment helped repair the intestinal barrier and modulated the gut microbial composition in T2DM mice, mainly facilitating the growth of short-chain fatty acid (SCFA)-producing bacteria, Spearman's analysis revealed these bacteria were positively related with the hypoglycemic efficacy of CSP. Colonic transcriptome analysis indicated the hypoglycemic effect of CSP was associated with the activation of the IGF1/PI3K/AKT signaling pathway. Correlative analysis revealed that this activation may result from the increase of SCFAs-producing bacteria by CSP. GC-MS detection verified that CSP treatment increased fecal SCFAs levels. Molecular docking revealed that SCFAs could bind with IGF1, PI3K, and AKT. Our findings demonstrated that CSP treatment modulates gut microbial composition, especially of the SCFAs-producing bacteria, activates the IGF1/PI3K/AKT signaling pathways, and exhibits hypoglycemic efficacy. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Xia, Ting AU - Xia T AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou 510515, PR China. FAU - Liu, Chang-Shun AU - Liu CS AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou 510515, PR China. FAU - Hu, Yan-Nan AU - Hu YN AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou 510515, PR China. FAU - Luo, Zhen-Ye AU - Luo ZY AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou 510515, PR China. FAU - Chen, Fei-Long AU - Chen FL AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou 510515, PR China. FAU - Yuan, Li-Xia AU - Yuan LX AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China. Electronic address: cnylxtcm@163.com. FAU - Tan, Xiao-Mei AU - Tan XM AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou 510515, PR China. Electronic address: tanxm_smu@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211004 PL - Canada TA - Food Res Int JT - Food research international (Ottawa, Ont.) JID - 9210143 RN - 0 (Fatty Acids, Volatile) RN - 0 (IGF1 protein, human) RN - 0 (Polysaccharides) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - *Coix/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - Fatty Acids, Volatile MH - *Gastrointestinal Microbiome MH - Humans MH - Insulin-Like Growth Factor I MH - Mice MH - Molecular Docking Simulation MH - Phosphatidylinositol 3-Kinases/metabolism MH - Polysaccharides/pharmacology MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction OTO - NOTNLM OT - 16S rRNA OT - Coix seed polysaccharides OT - Gut microbiota OT - IGF1/PI3K/AKT signaling pathway OT - SCFAs OT - T2DM OT - Transcriptomics EDAT- 2021/12/07 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/12/06 05:36 PHST- 2021/06/30 00:00 [received] PHST- 2021/09/01 00:00 [revised] PHST- 2021/09/13 00:00 [accepted] PHST- 2021/12/06 05:36 [entrez] PHST- 2021/12/07 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] AID - S0963-9969(21)00616-5 [pii] AID - 10.1016/j.foodres.2021.110717 [doi] PST - ppublish SO - Food Res Int. 2021 Dec;150(Pt A):110717. doi: 10.1016/j.foodres.2021.110717. Epub 2021 Oct 4.