Mohamed Reem Ali, Galal Omneya, Mohammed Ahmed Refaat, El-Abhar Hanan Salah
Department of Pharmacology and Toxicology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA) 26 July Mehwar Road Intersection with Wahat Road 6th October City Cairo 12566 Egypt
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University Cairo Egypt.
RSC Adv. 2018 Mar 27;8(22):11908-11920. doi: 10.1039/c7ra13105d. eCollection 2018 Mar 26.
Despite its known central effect, 5% of serotonin is found centrally, while around 95% is found peripherally. Serotonin is stored and co-released with insulin upon pancreatic islets stimulation by glucose. This fact raises the curiosity regarding its possible role in diabetes. Hence, in this study, we assessed the possible modulatory effects of tropisetron, a 5-HT3 receptor antagonist, on type 2 diabetes mellitus models in rats. The rats were allocated into two groups: normal and diabetic. The latter group was treated with metformin (500 mg kg, p.o.), tropisetron (1 and 2 mg kg, i.p.), and a combination of metformin and tropisetron (1 mg kg). The different treatment regimens corrected glucose and lipid homeostasis manifested by the decrease in serum levels of glucose, fructosamine, homeostasis model of insulin resistance, triglycerides, total cholesterol, free fatty acid, as well as receptor for advanced glycation end products. Additionally, the treatments elevated levels of insulin, serotonin, and homeostasis model of β-cell function. On the molecular level, treatments corrected the altered insulin signaling cascade (phosphorylated insulin receptor substrate 1, phosphorylated protein kinase B, and glucose transporter 4), and inhibited β-catenin and phosphorylated nuclear factor kappa B p65 in the assessed soleus skeletal muscle. A similar pattern was duplicated in the hippocampus. This study provided evidence for the role of tropisetron on type 2 diabetes mellitus modulating the insulin signaling cascade (insulin, phosphorylated insulin receptor substrate 1, phosphorylated protein kinase B, and glucose transporter 4), improving lipid/glucose profile, decreasing inflammatory markers (receptor for advanced glycation end products, and phosphorylated nuclear factor kappa B p65), as well as increasing 5-HT and reducing β-catenin.
尽管已知血清素具有中枢作用，但仅有5%的血清素存在于中枢，而约95%存在于外周。血清素在葡萄糖刺激胰岛时与胰岛素一起储存并共同释放。这一事实引发了人们对其在糖尿病中可能作用的好奇。因此，在本研究中，我们评估了5 - HT3受体拮抗剂托烷司琼对大鼠2型糖尿病模型的可能调节作用。大鼠被分为两组：正常组和糖尿病组。后一组分别用二甲双胍（500 mg/kg，口服）、托烷司琼（1和2 mg/kg，腹腔注射）以及二甲双胍与托烷司琼的组合（1 mg/kg）进行治疗。不同的治疗方案纠正了葡萄糖和脂质稳态，表现为血清葡萄糖、果糖胺、胰岛素抵抗稳态模型、甘油三酯、总胆固醇、游离脂肪酸以及晚期糖基化终产物受体水平的降低。此外，这些治疗提高了胰岛素、血清素和β细胞功能稳态模型的水平。在分子水平上，治疗纠正了改变的胰岛素信号级联反应（磷酸化胰岛素受体底物1、磷酸化蛋白激酶B和葡萄糖转运蛋白4），并在评估的比目鱼肌骨骼肌中抑制了β - 连环蛋白和磷酸化核因子κB p65。在海马体中也出现了类似的模式。本研究为托烷司琼在2型糖尿病中的作用提供了证据，它可调节胰岛素信号级联反应（胰岛素、磷酸化胰岛素受体底物1、磷酸化蛋白激酶B和葡萄糖转运蛋白4），改善脂质/葡萄糖谱，降低炎症标志物（晚期糖基化终产物受体和磷酸化核因子κB p65），以及增加5 - HT并减少β - 连环蛋白。
