National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China; Joint International Research Laboratory of Food & Medicine Resource Function, Henan Province, Kaifeng 475004, China.
Zhengzhou Mingze Pharmaceutical Technology Co., Ltd. Zhengzhou, 450000, China.
Biomed Pharmacother. 2020 May;125:109952. doi: 10.1016/j.biopha.2020.109952. Epub 2020 Feb 6.
Trelagliptin inhibits the enzyme dipeptidyl-4 (DPP-4) to treat type 2 diabetes and it may possess the potential to improve insulin resistance. However, the molecular mechanism is not known. In this study, the effect of trelagliptin succinate in improving insulin resistance was investigated. The differentiation system of 3T3-L1 mouse preadipocytes was used to determine the content of adipokines and the content of GLUT4 in the outer membrane. The expression of AKT, P-AKT, IRS-1 and P-IRS-1 in differentiated 3T3-L1 adipocytes was determined by western blotting. Our results demonstrated that trelagliptin succinate increased the expression of AKT, P-AKT, IRS-1 and P-IRS-1 in the PI-3K/AKT insulin signaling pathway. These events promote the trans-membrane function of GLUT4 and concomitant glucose intake in adipocytes. In addition, the secretion of free fatty acids and resistin were decreased. In conclusion, our study suggested that trelagliptin succinate improved insulin resistance in adipocytes via regulation of PI-3K/AKT/GLUT4 insulin signaling pathway.
替格列汀通过抑制二肽基肽酶-4（DPP-4）来治疗 2 型糖尿病，它可能具有改善胰岛素抵抗的潜力。然而，其分子机制尚不清楚。在这项研究中，研究了琥珀酸替格列汀改善胰岛素抵抗的作用。使用 3T3-L1 小鼠前脂肪细胞的分化系统来确定脂肪细胞因子的含量和外膜中 GLUT4 的含量。通过 Western blot 测定分化的 3T3-L1 脂肪细胞中 AKT、P-AKT、IRS-1 和 P-IRS-1 的表达。我们的结果表明，琥珀酸替格列汀增加了 PI-3K/AKT 胰岛素信号通路中 AKT、P-AKT、IRS-1 和 P-IRS-1 的表达。这些事件促进了 GLUT4 的跨膜功能和伴随的葡萄糖摄取。此外，游离脂肪酸和抵抗素的分泌减少。总之，我们的研究表明，琥珀酸替格列汀通过调节 PI-3K/AKT/GLUT4 胰岛素信号通路改善脂肪细胞中的胰岛素抵抗。
