PMID- 34699323 OWN - NLM STAT- MEDLINE DCOM- 20220218 LR - 20220218 IS - 2165-5987 (Electronic) IS - 2165-5979 (Print) IS - 2165-5979 (Linking) VI - 12 IP - 2 DP - 2021 Dec TI - Astragalus polysaccharide improve the proliferation and insulin secretion of mouse pancreatic beta cells induced by high glucose and palmitic acid partially through promoting miR-136-5p and miR-149-5p expression. PG - 9872-9884 LID - 10.1080/21655979.2021.1996314 [doi] AB - The current drugs for the treatment of type 2 diabetes mellitus (T2DM) can cause side effects after long-time use. Hence, the novel drugs were urgent need to developed for T2DM patients. In this study, the effect of astragalus polysaccharide on dysfunctional insulin cells was investigated to clarify whether astragalus polysaccharide could be a novel drug for T2DM treatment. MIN6 cells (mouse pancreatic beta-cell line) were treated with high glucose (HG)+ palmitic acid (PA) and then treated with astragalus polysaccharide. The proliferation, apoptosis, and insulin secretion were measured using CCK8, flow cytometry, and ELISA, respectively. Pancreatic and duodenal homeobox 1 (PDX1), miR-136-5p, and miR-149-5p expression levels were measured by RT-qPCR. The combination of EF-hand domain family member 2 (EFHD2) and miR-136-5p or miR-149-5p was analyzed by luciferase reporter assay. EFHD2 protein level was measured by western blot. We found that HG+PA treatment reduced MIN6 cell viability, insulin secretion, and PDX1 expression and promoted MIN6 cell apoptosis. Astragalus polysaccharide treatment reversed the effect of HG+PA on MIN6 cells. Additionally, astragalus polysaccharide treatment promoted miR-136-5p and miR-149-5p expression. Silencing of miR-136-5p and miR-149-5p expression partially reversed the therapeutic effects of astragalus polysaccharide. Furthermore, EFHD2 was the target of miR-136-5p and miR-149-5p. Meanwhile, astragalus polysaccharide treatment inhibited EFHD2 protein level in HG+PA treated MIN6 cell. Finally, EFHD2 overexpression partially reversed the therapeutic effects of astragalus polysaccharide. In conclusion, astragalus polysaccharide treatment improved proliferation and insulin secretion in HG+PA-treated MIN6 cells partially by promoting miR-136-5p and miR-149-5p expression to inhibit EFHD2 expression. FAU - Deng, Shifang AU - Deng S AD - Department of Traditional Chinese Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China. FAU - Yang, Lei AU - Yang L AD - Department of Geriatrics in Luohu Hospital of Traditional Chinese Medicine, Shenzhen Hospital of Shanghai University of traditional Chinese Medicine, Shenzhen, China. FAU - Ma, Ke AU - Ma K AD - Department of Traditional Chinese Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China. FAU - Bian, Wei AU - Bian W AD - Department of Traditional Chinese Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China. LA - eng PT - Journal Article PT - Video-Audio Media PL - United States TA - Bioengineered JT - Bioengineered JID - 101581063 RN - 0 (MIRN149 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Mirn136 microRNA, mouse) RN - 0 (Polysaccharides) RN - 2V16EO95H1 (Palmitic Acid) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Astragalus Plant/*chemistry MH - Cell Line MH - Cell Proliferation/*drug effects MH - Gene Expression Regulation/*drug effects MH - Glucose/*pharmacology MH - Insulin Secretion/*drug effects MH - Insulin-Secreting Cells/*metabolism MH - MicroRNAs/*biosynthesis MH - Palmitic Acid/*pharmacology MH - Polysaccharides/chemistry/*pharmacology PMC - PMC8810136 OTO - NOTNLM OT - Diabetes mellitus OT - Huang qi OT - Insulin-secreting Cells OT - MicroRNAs OT - Polysaccharides COIS- No potential conflict of interest was reported by the author(s). EDAT- 2021/10/27 06:00 MHDA- 2022/02/19 06:00 PMCR- 2021/12/07 CRDT- 2021/10/26 17:20 PHST- 2021/10/27 06:00 [pubmed] PHST- 2022/02/19 06:00 [medline] PHST- 2021/10/26 17:20 [entrez] PHST- 2021/12/07 00:00 [pmc-release] AID - 1996314 [pii] AID - 10.1080/21655979.2021.1996314 [doi] PST - ppublish SO - Bioengineered. 2021 Dec;12(2):9872-9884. doi: 10.1080/21655979.2021.1996314.