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KMID : 0616120220530030145
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Korean Journal of Pharmacognosy
2022 Volume.53 No. 3 p.145 ~ p.152
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Phillyrin Ameliorates Gluconeogenesis by Increasing the Phosphorylation of Akt and AMPK in Insulin Resistant HepG2 Cells
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Lee Seung-Yeon
Lee Gi-Ho
Kim Mi-Yeon
Chae Ju-Yeon
Kim Jae-Won
Jeong Hye-Gwang
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Abstract
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Type II diabetes mellitus (T2DM) is a chronic metabolic disease caused by insulin resistance, and abnormally elevated hepatic gluconeogenesis is characterized. Phillyrin, one of the major active constituents of Forsythia suspense, is known to possess the anti-inflammatory and anti-oxidant effects. However, the anti-diabetes mellitus effect of phillyrin and its molecular mechanisms are unclear. The aim of the current study was to investigate the role of phillyrin on gluconeogenesis in insulin resistant HepG2 cells. Phillyrin suppressed high glucose (HG)-induced glucose production. In addition, phillyrin reduced HG-induced the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), major genes in hepatic gluconeogenesis. Phillyrin treatment attenuated HG-induced nucleus protein levels of FOXO1 and HDAC5 and increased the phosphorylation of Akt, AMPK, HDAC5, and FOXO1. The block of AMPK and Akt activity did not exert the inhibitory effect of phillyrin on gluconeogenesis in insulin resistant HepG2. Taken together, these results suggest that phillyrin inhibits gluconeogenesis of hepatocytes to improve glucose metabolism, through the regulation of LKB1/AMPK/HDAC5 and PI3K/AKT/FOXO1 pathway. These results indicate that phillyrin may be useful in improving hepatic gluconeogenesis associated with insulin resistant and T2DM.
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KEYWORD
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Phillyrin, Gluconeogenesis, FOXO1, Akt, AMPK
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