Foxtail millet, as a leading variety in arid and semi-arid areas of Asia and Africa, can provide broad potential benefits to human health. However, its digestion properties have not been reported. So in this study, the in vitro starch digestibilities and in vivo glycemic indices (GI) of foxtail millet and pure millet products were investigated. The results showed that starch digestibility of the foxtail millet flour is obviously lower than that of wheat flour. However, deproteinization and heating significantly increased its rapidly digestible starch and decreased its slowly digestible starch and resistant starch. The GIs of pure millet products were in the following order: millet porridge (93.6 ± 11.3) > millet steamed bread (89.6 ± 8.8) > No. 1 millet pancake (75.0% millet flour and 25.0% extrusion flour, 83.0 ± 9.6) > No. 2 millet pancake (without extrusion flour, 76.2 ± 10.7) > cooked millet (64.4 ± 8.5). They were significantly positively correlated with the rapidly digestible starch (r = 0.959), degree of gelatinization (r = 0.967) and estimated glycemic index (r = 0.988). Both in vitro and in vivo tests suggested that boiling, steaming and extrusion enhanced the formation of digestible starch and subsequently increased the GI values. Additionally, the No. 1 millet pancake and cooked millet had a relatively gentle stimulation on β-cell. Therefore, foxtail millet, especially the cooked millet, may serve as a potential source of nutraceutical and functional food that could delay the development of type 2 diabetes.

Foxtail millet has relatively low starch digestibility and moderate glycemic index compared to other grains. Since there are still no clinical researches regarding its long-term effect on blood glucose, this self-controlled study was conducted to investigate the glucose-lowering effect of foxtail millet in free-living subjects with impaired glucose tolerance (IGT). Fifty g/day of foxtail millet was provided to enrolled subjects throughout 12 weeks and the related clinical parameters were investigated at week 0, 6 and 12, respectively. After 12 weeks of foxtail millet intervention, the mean fasting blood glucose of the subjects decreased from 5.7 ± 0.9 mmol/L to 5.3 ± 0.7 mmol/L (p < 0.001) and the mean 2 h-glucose decreased from 10.2 ± 2.6 mmol/L to 9.4 ± 2.3 mmol/L (p = 0.003). The intake of foxtail millet caused a significant increase of serum leptin (p = 0.012), decrease of insulin resistance (p = 0.007), and marginal reduction of inflammation. Furthermore, a sex-dependent difference in glucose-lowering effect of foxtail millet was observed in this study. Foxtail millet could improve the glycemic control in free-living subjects with IGT, suggesting that increasing the consumption of foxtail millet might be beneficial to individuals suffering from type 2 diabetes mellitus.

Foxtail millet (FM) is receiving ongoing increased attention due to its beneficial health effects, including the hypoglycemic effect. However, the underlying mechanisms of the hypoglycemic effect have been underexplored. In the present study, the hypoglycemic effect of FM supplementation was confirmed again in high-fat diet and streptozotocin-induced diabetic rats with significantly decreased fasting glucose (FG), glycated serum protein, and areas under the glucose tolerance test (p < 0.05). We employed 16S rRNA and liver RNA sequencing technologies to identify the target gut microbes and signaling pathways involved in the hypoglycemic effect of FM supplementation. The results showed that FM supplementation significantly increased the relative abundance of Lactobacillus and Ruminococcus_2, which were significantly negatively correlated with FG and 2-h glucose. FM supplementation significantly reversed the trends of gene expression in diabetic rats. Specifically, FM supplementation inhibited gluconeogenesis, stimulated glycolysis, and restored fatty acid synthesis through activation of the PI3K/AKT signaling pathway. FM also reduced inflammation through inhibition of the NF-κB signaling pathway. Spearman’s correlation analysis indicated a complicated set of interdependencies among the gut microbiota, signaling pathways, and metabolic parameters. Collectively, the above results suggest that the hypoglycemic effect of FM was at least partially mediated by the increased relative abundance of Lactobacillus, activation of the PI3K/AKT signaling pathway, and inhibition of the NF-κB signaling pathway.