Phloridzin Acts as an Inhibitor of Protein-Tyrosine Phosphatase MEG2 Relevant to Insulin Resistance

被引:10
|
作者
Yoon, Sun-Young [1 ,2 ]
Yu, Jae Sik [1 ]
Hwang, Ji Young [1 ]
So, Hae Min [1 ]
Seo, Seung Oh [1 ]
Kim, Jung Kyu [3 ]
Jang, Tae Su [4 ]
Chung, Sang J. [1 ]
Kim, Ki Hyun [1 ]
机构
[1] Sungkyunkwan Univ, Sch Pharm, Suwon 16419, South Korea
[2] Kwangju Womens Univ, Dept Cosmet Sci, Gwangju 62396, South Korea
[3] Sungkyunkwan Univ, Sch Chem Engn, Suwon 16419, South Korea
[4] Dankook Univ, Dept Med, Cheonan 31116, Chungnam, South Korea
来源
MOLECULES | 2021年 / 26卷 / 06期
基金
新加坡国家研究基金会;
关键词
protein tyrosine phosphatases (PTPs); PTP-MEG2; phloridzin; type; 2; diabetes; glucose-uptake;
D O I
10.3390/molecules26061612
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inhibition of the megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2, also named PTPN9) activity has been shown to be a potential therapeutic strategy for the treatment of type 2 diabetes. Previously, we reported that PTP-MEG2 knockdown enhances adenosine monophosphate activated protein kinase (AMPK) phosphorylation, suggesting that PTP-MEG2 may be a potential antidiabetic target. In this study, we found that phloridzin, isolated from Ulmus davidiana var. japonica, inhibits the catalytic activity of PTP-MEG2 (half-inhibitory concentration, IC50 = 32 +/- 1.06 mu M) in vitro, indicating that it could be a potential antidiabetic drug candidate. Importantly, phloridzin stimulated glucose uptake by differentiated 3T3-L1 adipocytes and C2C12 muscle cells compared to that by the control cells. Moreover, phloridzin led to the enhanced phosphorylation of AMPK and Akt relevant to increased insulin sensitivity. Importantly, phloridzin attenuated palmitate-induced insulin resistance in C2C12 muscle cells. We also found that phloridzin did not accelerate adipocyte differentiation, suggesting that phloridzin improves insulin sensitivity without significant lipid accumulation. Taken together, our results demonstrate that phloridzin, an inhibitor of PTP-MEG2, stimulates glucose uptake through the activation of both AMPK and Akt signaling pathways. These results strongly suggest that phloridzin could be used as a potential therapeutic candidate for the treatment of type 2 diabetes.
引用
收藏
页数:15
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