Diosmetin ameliorates glucose metabolism in KK-Ay diabetic mice through
regulation of Corynebacterium glutamicum via IRS/PI3K/ AKT signaling
Background and Purpose: Diosmetin (Dios), a flavonoid compound with
multiple pharmacological activities. However, fewer studies have
reported its effects on diabetes. Here, we address the effect of Dios on
glucose metabolism and gut microbiota in KK-Ay diabetic mice.
Experimental Approach: Wild type C57BL/6J mice or diabetic KK-Ay mice
were treated with vehicle or Dios for one month. The liver RNA-Seq was
used to reveal the key signaling pathway interfered with Dios. The liver
16S rRNA gene sequencing was used to reveal the effects of Dios on gut
microbiota. The experiment of C. glu transplantation was used to reveal
the relationship between Dios and C. glu on glucose metabolism. Key
Results: Dios treatment significantly decreased blood glucose and
increased serum insulin concentrations. Transcriptome sequencing
analysis found that the underlining mechanism of diosmetin on T2DM by
regulating signal pathways of 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 can markedly
ameliorate glucose metabolism by up-regulating IRS/PI3K/AKT signaling
pathway to promoting glycogen synthesis and GLUT4 translocation.
Conclusions and Implications: Dios treatment remarkably ameliorated
glucose metabolism in KK-Ay diabetic mice by the regulation of C. glu on
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.