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This work aimed to investigate the hypoglycemic effects and underlying mechanism of whole grain proso millet (Panicum miliaceum L.; WPM) on type 2 diabetes mellitus (T2DM). The results showed that WPM 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, WPM significantly inhibited the expression of gluconeogenesis-related genes G6pase, Pepck, Foxo1, and Pgc -1α. Further study by miRNA high-throughput sequencing revealed that WPM supplementation mainly altered the liver miRNA expression profile of T2DM mice by increasing 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. GO and KEGG analyses showed that the target genes of these miRNAs were mainly enriched in the PI3K/AKT signaling pathway. WPM supplementation significantly increased the level of PI3K, p-AKT, and GSK3β in the liver of T2DM mice. Taken together, WPM exerts antidiabetic effects by improving the miRNA profile and activating the PI3K/AKT signaling pathway to inhibit gluconeogenesis. This study implies that PM can act as a dietary supplement to attenuate T2DM.

The prevalence of type 2 diabetes has been growing at an increasing rate worldwide. Dietary therapy is probably the easiest and least expensive method to prevent and treat diabetes. Previous studies have reported that coarse grains have anti‐diabetic effects. Although considerable efforts have been made on the anti‐diabetic function of different grains, the mechanisms of coarse grains on type 2 diabetes have not been systematically compared and summarized so far. Intestinal flora, reported as the main ‘organ’ of action underlying coarse grains, is an important factor in the alleviation of type 2 diabetes by coarse grains. Furthermore, microRNA (miRNA), as a new disease marker and ‘dark nutrient’, plays a likely influential role in cross‐border communication among coarse grains, intestinal flora, and hosts. Given this context, this article reviews several possible mechanisms for the role of coarse grains on diabetes, incorporating resistance to inflammation and oxidative stress, repair of insulin signaling and β‐cell dysfunction, and highlights the regulation of intestinal flora disorders and miRNAs expression, along with some novel insights. © 2022 Society of Chemical Industry.