Diosmetin ameliorate type 2 diabetic mellitus by up-regulating Corynebacterium glutamicum to regulate IRS/PI3K/AKT-mediated glucose metabolism disorder in KK-Ay mice

作者全名：Gong Xiaobao; Xiong Li; Bi Caihong; Zhang Baoshun

作者地址："[Gong Xiaobao; Zhang Baoshun] Southwest Univ, Coll Pharmaceut Sci, 2 Tiansheng Rd, Chongqing 400716, Peoples R China; [Xiong Li] Chongqing Med Univ, Dept Pharm, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Bi Caihong] Serv Ctr Technol Extens Linyi Fruit & Tea, Linyi 276000, Shandong, Peoples R China"

通信作者："Zhang, BS (corresponding author), Southwest Univ, Coll Pharmaceut Sci, 2 Tiansheng Rd, Chongqing 400716, Peoples R China."

来源：PHYTOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000661278000017

JCR分区：Q1

影响因子：7.9

年份：2021

卷号：87

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Diosmetin; T2DM; Gut microbiota; Glucose metabolism; Corynebacterium glutamicum; IRS/PI3K/AKT signaling pathway

摘要："Background and purpose: 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. Method: 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. Results: 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. Conclusions: 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."

基金机构："Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [XDJK2020B056]; National Key Research and Development Program of China for Traditional Chinese Medicine Modernization [2017YFC1702605, 2017YFC1702606]"

基金资助正文："This work was supported by the Fundamental Research Funds for the Central Universities (XDJK2020B056), and the National Key Research and Development Program of China for Traditional Chinese Medicine Modernization (2017YFC1702605, 2017YFC1702606)."