Abstract
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.
Highlights
Compared with diabetic control (DC) rats, the FBG concentration, GSP concentration, and areas under the glucose tolerance tests (GTTs) (AUC) of Foxtail millet (FM) rats were significantly decreased, while the total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) concentration were significantly increased after 4 weeks of FM supplementation
There were no significant differences in the concentrations of the FBG, TC, and HDL-C between the NC and FM groups (Figure 1A,D,F,J,K)
The blood glucose concentration of FM rats was still higher than that of NC rats throughout GTT, the concentration decreased significantly at 0, 60, and 120 min when compared with DC rats (Figure 1E)
Summary
Diabetes and its associated disorders have reached an alarming level worldwide. In. 2019, an estimated 463 million adults aged 20–79 years old worldwide had diabetes, and by 2045, 700 million adults will be living with diabetes [1]. Type 2 diabetes (T2D) accounts for the vast majority of diabetes. Recent decades have seen an exponential increase in the number of people suffering from T2D, despite the expanding number of anti-hyperglycemic medication options [2]. There is firm evidence that T2D can be prevented and effectively managed through the adoption of healthy lifestyles [1], including the increased consumption of whole grains [3]
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