College of Pharmaceutical Sciences, Southwest University, No.2 Tiansheng Road, Beibei, Chongqing 400716, PR China.
Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Phytomedicine. 2021 Jul;87:153582. doi: 10.1016/j.phymed.2021.153582. Epub 2021 Jun 3.
Diosmetin (Dios), a flavonoid compound with multiple pharmacological activities. However, fewer studies have reported its effects on type 2 diabetic mellitus (T2DM). Here, we address the effect of Dios on glucose metabolism and gut microbiota in KK-Ay diabetic mice.
Wild type C57BL/6 J mice or diabetic KK-Ay mice were treated with vehicle or Dios for one month. The ELISA kit and fluorescence microscope system were respectively employed to the evaluation of serum biochemical indicators and histopathological changes. Liver RNA-Seq and western blot were used to reveal the key signaling pathway. The effects of Dios on gut microbiota was investigated by the 16S rRNA gene sequencing, as well as the relationship between Dios and C. glu on glucose metabolism was explored with the C. glu transplantation.
Dios treatment significantly decreased blood glucose and increased serum insulin concentrations. RNA-Seq analysis found that the underlying action mechanism of Dios on T2DM was via modulating glucose metabolism, which was proved by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. Besides, Dios treatment reshaped the unbalanced gut microbiota by suppressing the ratio of Firmicutes/Bacteroidetes and markedly increasing the richness of C. glu. Moreover, treatment with C. glu and Dios together could markedly ameliorate glucose metabolism by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation.
Dios treatment remarkably ameliorated glucose metabolism in KK-Ay diabetic mice by the regulation of C. glu via IRS/PI3K/AKT signaling pathway and reshaped the unbalanced gut microbiota. Our study provided evidence for the application of Dios to the treatment of T2DM.
地奥司明（Dios）是一种具有多种药理活性的类黄酮化合物。然而，关于其对 2 型糖尿病（T2DM）的影响的研究较少。在这里，我们研究了地奥司明对 KK-Ay 糖尿病小鼠葡萄糖代谢和肠道微生物群的影响。
用 vehicle 或 Dios 处理野生型 C57BL/6 J 小鼠或糖尿病 KK-Ay 小鼠一个月。分别采用 ELISA 试剂盒和荧光显微镜系统评估血清生化指标和组织病理学变化。肝 RNA-Seq 和 western blot 用于揭示关键信号通路。16S rRNA 基因测序用于研究 Dios 对肠道微生物群的影响，并通过 C. glu 移植探索 Dios 与 C. glu 对葡萄糖代谢的关系。
Dios 处理显著降低血糖并增加血清胰岛素浓度。RNA-Seq 分析发现，Dios 对 T2DM 的作用机制是通过调节葡萄糖代谢，这通过上调 IRS/PI3K/AKT 信号通路来促进糖原合成和 GLUT4 易位得到证实。此外，Dios 处理通过抑制厚壁菌门/拟杆菌门的比例和显著增加 C. glu 的丰富度来重塑失衡的肠道微生物群。此外，同时用 C. glu 和 Dios 处理可以通过上调 IRS/PI3K/AKT 信号通路来促进糖原合成和 GLUT4 易位来显著改善葡萄糖代谢。
Dios 通过 IRS/PI3K/AKT 信号通路调节 C. glu 显著改善 KK-Ay 糖尿病小鼠的葡萄糖代谢，并重塑失衡的肠道微生物群。我们的研究为 Dios 在 T2DM 治疗中的应用提供了证据。
