Hypoglycemic effect of astragaloside IV via modulating gut microbiota and regulating AMPK/SIRT1 and PI3K/AKT pathway

2021 ◽  
Vol 281 ◽  
pp. 114558
Author(s):  
Pin Gong ◽  
Xuyang Xiao ◽  
Shuang Wang ◽  
Fuxiong Shi ◽  
Ni Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Hypoglycemic Effect ◽  
Akt Pathway ◽  
Astragaloside Iv

scholarly journals Hypoglycemic Effect of Prolamin from Cooked Foxtail Millet (Setaria italic) on Streptozotocin-Induced Diabetic Mice

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3452
Author(s):  
Yongxia Fu ◽  
Ruiyang Yin ◽  
Zhenyu Liu ◽  
Yan Niu ◽  
Erhu Guo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Foxtail Millet ◽  
Hypoglycemic Effect ◽  
Rrna Gene ◽  
Serotonin Level ◽  
Glucose Metabolism Disorders ◽  
Sequencing Analysis ◽  
Diabetic Mice ◽  
Serum Metabolomics

Millet proteins have been demonstrated to possess glucose-lowering and lipid metabolic disorder modulation functions against diabetes; however, the molecular mechanisms underlying their anti-diabetic effects remain unclear. The present study aimed to investigate the hypoglycemic effect of prolamin from cooked foxtail millet (PCFM) on type 2 diabetic mice, and explore the gut microbiota and serum metabolic profile changes that are associated with diabetes attenuation by PCFM. Our diabetes model was established using a high-fat diet combined with streptozotocin before PCFM or saline was daily administrated by gavage for 5 weeks. The results showed that PCFM ameliorated glucose metabolism disorders associated with type 2 diabetes. Furthermore, the effects of PCFM administration on gut microbiota and serum metabolome were investigated. 16S rRNA gene sequencing analysis indicated that PCFM alleviated diabetes-related gut microbiota dysbiosis in mice. Additionally, the serum metabolomics analysis revealed that the metabolite levels disturbed by diabetes were partly altered by PCFM. Notably, the decreased D-Glucose level caused by PCFM suggested that its anti-diabetic potential can be associated with the activation of glycolysis and the inhibition of gluconeogenesis, starch and sucrose metabolism and galactose metabolism. In addition, the increased serotonin level caused by PCFM may stimulate insulin secretion by pancreatic β-cells, which contributed to its hypoglycemic effect. Taken together, our research demonstrated that the modulation of gut microbiota composition and the serum metabolomics profile was associated with the anti-diabetic effect of PCFM.

scholarly journals Protective Effects of Astragaloside IV on Uric Acid-Induced Pancreatic β-Cell Injury through PI3K/AKT Pathway Activation

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Zhenhuan Jiang ◽  
Gang Wang ◽  
Lingling Meng ◽  
Yunzhao Tang ◽  
Min Yang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Insulin Secretion ◽  
Akt Pathway ◽  
Dependent Manner ◽  
Protective Effects ◽  
Pancreatic Β Cell ◽  
Astragaloside Iv ◽  
Β Cell ◽  
Min6 Cells ◽  
Dose Dependent

Background. Elevated uric acid (UA) has been found to damage pancreatic β-cell, promote oxidative stress, and cause insulin resistance in type 2 diabetes (T2D). Astragaloside IV (AS-IV), a major active monomer extracted from Astragalus membranaceus (Fisch.) Bunge. which belongs to TRIB. Galegeae (Br.) Torrey et Gray, Papilionaceae, exhibits various activities in a pathophysiological environment and has been widely employed to treat diseases. However, the effects of AS-IV on UA-induced pancreatic β-cell damage need to be investigated and the associating mechanism needs to be elucidated. This study was designed to determine the protective effects and underlying mechanism of AS-IV on UA-induced pancreatic β-cell dysfunction in T2D. Methods. UA-treated Min6 cells were exposed to AS-IV or wortmannin. Thereafter, the 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and flow cytometry were employed to determine the effect of AS-IV on cell proliferation and apoptosis, respectively. Insulin secretion was evaluated using the glucose-stimulated insulin secretion (GSIS) assay. Finally, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to determine the effect of AS-IV on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in UA-treated cells. Results. AS-IV had no cytotoxic effects on Min6 cells. UA significantly suppressed Min6 cell growth, promoted cell apoptosis, and enhanced caspase-3 activity; however, AS-IV abolished these effects in a dose-dependent manner. Further, decreased insulin secretion was found in UA-treated Min6 cells compared to control cells, and the production of insulin was enhanced by AS-IV in a dose-dependent manner. AS-IV significantly increased phosphorylated (p)-AKT expression and the ratio of p-AKT/AKT in Min6 cells exposed to UA. No evident change in AKT mRNA level was found in the different groups. However, the effects of AS-IV on UA-stimulated Min6 cells were reversed by 100 nM wortmannin. Conclusion. Collectively, our data suggest that AS-IV protected pancreatic β-cells from UA-treated dysfunction by activating the PI3K/AKT pathway. Such findings suggest that AS-IV may be an efficient natural agent against T2D.

scholarly journals Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1837
Author(s):  
Xin Ren ◽  
Linxuan Wang ◽  
Zenglong Chen ◽  
Dianzhi Hou ◽  
Yong Xue ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Relative Abundance ◽  
Foxtail Millet ◽  
Acid Synthesis ◽  
Akt Signaling ◽  
Diabetic Rats ◽  
Hypoglycemic Effect ◽  
Akt Signaling Pathway

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.

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