黄芪多糖通过促进 miR-136-5p 和 miR-149-5p 的表达部分改善高糖和棕榈酸诱导的小鼠胰岛β细胞的增殖和胰岛素分泌。
Astragalus polysaccharide improve the proliferation and insulin secretion of mouse pancreatic β cells induced by high glucose and palmitic acid partially through promoting miR-136-5p and miR-149-5p expression.
机构信息
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.
Department of Geriatrics in Luohu Hospital of Traditional Chinese Medicine, Shenzhen Hospital of Shanghai University of traditional Chinese Medicine, Shenzhen, China.
出版信息
Bioengineered. 2021 Dec;12(2):9872-9884. doi: 10.1080/21655979.2021.1996314.
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 β-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.
目前用于治疗 2 型糖尿病（T2DM）的药物长期使用后会产生副作用。因此，急需开发新型药物用于 T2DM 患者的治疗。本研究旨在探讨黄芪多糖对功能失调的胰岛素细胞的作用，以明确黄芪多糖是否可成为治疗 T2DM 的新型药物。将 MIN6 细胞（小鼠胰岛β细胞系）用高葡萄糖（HG）+棕榈酸（PA）处理，然后用黄芪多糖处理。用 CCK8、流式细胞术和 ELISA 分别测定细胞增殖、凋亡和胰岛素分泌情况。用 RT-qPCR 测定胰腺十二指肠同源盒 1（PDX1）、miR-136-5p 和 miR-149-5p 的表达水平。通过荧光素酶报告基因检测分析 EF 手结构域家族成员 2（EFHD2）与 miR-136-5p 或 miR-149-5p 的结合情况。用 Western blot 测定 EFHD2 蛋白水平。结果发现，HG+PA 处理降低 MIN6 细胞活力、胰岛素分泌和 PDX1 表达，促进 MIN6 细胞凋亡。黄芪多糖处理可逆转 HG+PA 对 MIN6 细胞的作用。此外，黄芪多糖处理可促进 miR-136-5p 和 miR-149-5p 的表达。沉默 miR-136-5p 和 miR-149-5p 的表达可部分逆转黄芪多糖的治疗作用。EFHD2 是 miR-136-5p 和 miR-149-5p 的靶基因。同时，黄芪多糖处理可抑制 HG+PA 处理的 MIN6 细胞中 EFHD2 蛋白水平。最后，EFHD2 过表达部分逆转了黄芪多糖的治疗作用。综上，黄芪多糖处理通过促进 miR-136-5p 和 miR-149-5p 表达抑制 EFHD2 表达，从而部分改善 HG+PA 处理的 MIN6 细胞的增殖和胰岛素分泌。
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