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Ginseng-derived GABAFG ameliorates type 2 diabetes mellitus by modulating autophagy-lysosome pathway and gut
Meng-Han Qi1, Hai-Yan Zhang1, Yun-Yi Hou1
1College of Chinese Medicinal Materials, Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
Introduction:
Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear.
Objectives:
To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment.
Methods:
The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells (in vivo and in vitro) were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput sequencing and serum metabolomics.
Results:
GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells in vitro. Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased Akkermansia, decreased Romboutsia abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia.
Conclusion:
This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic diseases.
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