Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota
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 confirm...
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doaj-8b363d3e4edd4193bb2d9883dd63ffd52021-06-01T01:22:24ZengMDPI AGNutrients2072-66432021-05-01131837183710.3390/nu13061837Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut MicrobiotaXin Ren0Linxuan Wang1Zenglong Chen2Dianzhi Hou3Yong Xue4Xianmin Diao5Qun Shen6Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, ChinaState Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, ChinaKey Laboratory of Plant Protein and Grain Processing, National Engineering and Technology Research Center for Fruits and Vegetables, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaKey Laboratory of Plant Protein and Grain Processing, National Engineering and Technology Research Center for Fruits and Vegetables, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaCenter for Crop Germplasm Resources, Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, ChinaKey Laboratory of Plant Protein and Grain Processing, National Engineering and Technology Research Center for Fruits and Vegetables, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaFoxtail 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 (<i>p</i> < 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.https://www.mdpi.com/2072-6643/13/6/1837foxtail milletglucose metabolismgut microbiotaPI3K/AKT signaling pathwayNF-κB signaling pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xin Ren Linxuan Wang Zenglong Chen Dianzhi Hou Yong Xue Xianmin Diao Qun Shen |
spellingShingle |
Xin Ren Linxuan Wang Zenglong Chen Dianzhi Hou Yong Xue Xianmin Diao Qun Shen Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota Nutrients foxtail millet glucose metabolism gut microbiota PI3K/AKT signaling pathway NF-κB signaling pathway |
author_facet |
Xin Ren Linxuan Wang Zenglong Chen Dianzhi Hou Yong Xue Xianmin Diao Qun Shen |
author_sort |
Xin Ren |
title |
Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota |
title_short |
Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota |
title_full |
Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota |
title_fullStr |
Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota |
title_full_unstemmed |
Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota |
title_sort |
foxtail millet improves blood glucose metabolism in diabetic rats through pi3k/akt and nf-κb signaling pathways mediated by gut microbiota |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2021-05-01 |
description |
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 (<i>p</i> < 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. |
topic |
foxtail millet glucose metabolism gut microbiota PI3K/AKT signaling pathway NF-κB signaling pathway |
url |
https://www.mdpi.com/2072-6643/13/6/1837 |
work_keys_str_mv |
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