Gone Geetanjali B, Go Geonhui, Nam Gibeom, Jeong Woojoo, Kim Hyemin, Lee Soah, Chung Sang J
Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Nutrients. 2024 Feb 25;16(5):647. doi: 10.3390/nu16050647.
Protein tyrosine phosphatases (PTPs) are pivotal contributors to the development of type 2 diabetes (T2DM). Hence, directing interventions towards PTPs emerges as a valuable therapeutic approach for managing type 2 diabetes. In particular, PTPN6 and PTPN9 are targets for anti-diabetic effects. Through high-throughput drug screening, quercetagitrin (QG) was recognized as a dual-target inhibitor of PTPN6 and PTPN9. We observed that QG suppressed the catalytic activity of PTPN6 (IC = 1 μM) and PTPN9 (IC = 1.7 μM) in vitro and enhanced glucose uptake by mature C2C12 myoblasts. Additionally, QG increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-dependent phosphorylation of Akt in mature C2C12 myoblasts. It further promoted the phosphorylation of Akt in the presence of palmitic acid, suggesting the attenuation of insulin resistance. In summary, our results indicate QG's role as a potent inhibitor targeting both PTPN6 and PTPN9, showcasing its potential as a promising treatment avenue for T2DM.
蛋白酪氨酸磷酸酶（PTPs）是2型糖尿病（T2DM）发病的关键因素。因此，针对PTPs进行干预成为治疗2型糖尿病的一种有价值的治疗方法。特别是，PTPN6和PTPN9是具有抗糖尿病作用的靶点。通过高通量药物筛选，槲皮苷（QG）被鉴定为PTPN6和PTPN9的双靶点抑制剂。我们观察到，QG在体外抑制了PTPN6（IC = 1 μM）和PTPN9（IC = 1.7 μM）的催化活性，并增强了成熟C2C12成肌细胞的葡萄糖摄取。此外，QG增加了成熟C2C12成肌细胞中腺苷单磷酸激活蛋白激酶（AMPK）的磷酸化以及Akt的胰岛素依赖性磷酸化。在棕榈酸存在的情况下，它进一步促进了Akt的磷酸化，表明胰岛素抵抗得到缓解。总之，我们的结果表明QG作为一种强效抑制剂，同时靶向PTPN6和PTPN9，展示了其作为T2DM一种有前景的治疗途径的潜力。
