Aldakinah Amat-Alrazaq A, Al-Shorbagy Muhammad Y, Abdallah Dalaal M, El-Abhar Hanan S
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
J Pharm Pharmacol. 2017 Jul;69(7):856-864. doi: 10.1111/jphp.12713. Epub 2017 Mar 8.
Trigonelline (TRG) is known to have an antidiabetic efficacy; however, its mechanism is not entirely elucidated.
Hence, its effect on insulin signaling, besides its effectiveness in combination with vildagliptin (VLD) in a Type 2 diabetes model has been tested.
TRG (50 mg/kg; p.o) lowered serum glucose, fructosamine, insulin, and HOMA-IR index and increased insulin sensitivity in soleus muscle via augmenting insulin receptor autophosphorylation (IR-PH), pT308-Akt, and glucose transporter 4 (GLUT4). Additionally, it reduced muscle advanced glycation end products and lipid peroxides with increased glutathione. TRG showed an anti-lipidemic effect lowering serum and/or muscle total cholesterol, triglycerides, and FFAs to decrease body weight, and visceral/epididymal indices. Furthermore, VLD (3 and 10 mg/kg, p.o) increased IR-PH, pT308-Akt, and GLUT4 to improve insulin signaling. The combined effect of TRG with the low dose of VLD was mostly confined to the reduction of the aberrant lipid profile.
The beneficial effect of TRG on insulin sensitivity and glucose/ lipid homeostasis is mediated by the enhancement of the insulin signaling and antioxidant property. Moreover, the positive impact of VLD on pT308-Akt is an integral part in insulin signaling, and hence its antidiabetic effect.
已知胡芦巴碱（TRG）具有抗糖尿病功效；然而，其作用机制尚未完全阐明。
因此，除了在2型糖尿病模型中测试其与维格列汀（VLD）联合使用的有效性外，还测试了其对胰岛素信号传导的影响。
TRG（50mg/kg；口服）通过增强胰岛素受体自身磷酸化（IR-PH）、pT308-Akt和葡萄糖转运蛋白4（GLUT4）降低血清葡萄糖、果糖胺、胰岛素和HOMA-IR指数，并增加比目鱼肌中的胰岛素敏感性。此外，它还减少了肌肉晚期糖基化终产物和脂质过氧化物，同时增加了谷胱甘肽。TRG显示出抗血脂作用，降低血清和/或肌肉总胆固醇、甘油三酯和游离脂肪酸，从而减轻体重以及降低内脏/附睾指数。此外，VLD（3和10mg/kg，口服）增加IR-PH、pT308-Akt和GLUT4以改善胰岛素信号传导。TRG与低剂量VLD的联合作用主要局限于改善异常血脂谱。
TRG对胰岛素敏感性和葡萄糖/脂质稳态的有益作用是通过增强胰岛素信号传导和抗氧化特性介导的。此外，VLD对pT308-Akt的积极影响是胰岛素信号传导的一个组成部分，因此也是其抗糖尿病作用的一部分。
