Whole Grain Proso Millet (Panicum miliaceum L.) Attenuates Hyperglycemia in Type 2 Diabetic Mice: Involvement of miRNA Profile

Thiswork aimed to investigate the hypoglycemic effects and underlyingmechanism of whole grain proso millet (Panicum miliaceum L.; WPM) on type 2 diabetes mellitus (T2DM). The results showed thatWPM supplementation significantly reduced fasting blood glucose (FBG)and serum lipid levels in T2DM mice induced by a high-fat diet (HFD)combined with streptozotocin (STZ), with improved glucose tolerance,liver and kidney injury, and insulin resistance. In addition, WPMsignificantly inhibited the expression of gluconeogenesis-relatedgenes G6pase, Pepck, Foxo1, and Pgc -1 alpha. Further studyby miRNA high-throughput sequencing revealed that WPM supplementationmainly altered the liver miRNA expression profile of T2DM mice byincreasing the expression of miR-144-3p_R-1 and miR-423-5p,reducing the expression of miR-22-5p_R-1 and miR-30a-3p. GOand KEGG analyses showed that the target genes of these miRNAs weremainly enriched in the PI3K/AKT signaling pathway. WPM supplementationsignificantly increased the level of PI3K, p-AKT, and GSK3 beta in the liver of T2DM mice. Taken together, WPM exerts antidiabeticeffects by improving the miRNA profile and activating the PI3K/AKTsignaling pathway to inhibit gluconeogenesis. This study implies thatPM can act as a dietary supplement to attenuate T2DM.