Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India.
Central Research Laboratory, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India.
Eur J Pharmacol. 2020 Apr 15;873:173004. doi: 10.1016/j.ejphar.2020.173004. Epub 2020 Feb 8.
In our previous study, we have shown that β-sitosterol (SIT) enhances glycemic control by increasing the activation of insulin receptor (IR) and glucose transporter 4 (GLUT4) proteins in adipose tissue. However, the possible role of SIT on the regulation of post-receptor insulin signal transduction is not known. Hence, the study was aimed to assess the effects of SIT on IRS-1/Akt mediated insulin signaling molecules in high-fat diet and sucrose induced type-2 diabetic rats. An oral effective dose of SIT (20 mg/kg b.wt) was given for 30 days to high fat-fed type-2 diabetic rats to find out whether SIT regulates IRS-1/Akt pathway of insulin signaling. The results showed that SIT attenuated the insulin receptor substrate-1 serine phosphorylation (p-IRS-1) (P = 0.0003). However, it up-regulated the mRNA expression of IR (P = 0.0036) and post-receptor insulin signaling molecules such as IRS-1 (P < 0.0001), β-arrestin-2 (P < 0.0058), Akt (P = 0.0008), AS160 (P = 0.0030) and GLUT4 (P < 0.0001) with a concomitant increase in the levels of IRS-1(P < 0.0001), p-IRS1-1 (P = 0.0014), Akt (P < 0.0001), p-Akt (P = 0.0006; P < 0.0001), AS160 and p-AS160 (P < 0.0001) compared with type-2 diabetic rats. In Silico analysis was also performed and it showed that SIT possesses the greater binding affinity with β-arrestin-2, c-Src, and IRS-1 as well as Akt proteins and proved to attenuate insulin resistance as this study coincides with in vivo findings. Our present study clearly shows that SIT attenuates high fat diet-induced detrimental changes in adipose tissue. Therefore, it is concluded from the present findings that, SIT could be used as potential therapeutic phytomedicine for the management of type-2 diabetes.
在我们之前的研究中，我们已经表明β-谷甾醇（SIT）通过增加脂肪组织中胰岛素受体（IR）和葡萄糖转运蛋白 4（GLUT4）蛋白的激活来增强血糖控制。然而，SIT 对受体后胰岛素信号转导的调节作用尚不清楚。因此，本研究旨在评估 SIT 对高脂肪饮食和蔗糖诱导的 2 型糖尿病大鼠 IRS-1/Akt 介导的胰岛素信号分子的影响。给予口服有效剂量的 SIT（20mg/kg bw）30 天，以找出 SIT 是否调节胰岛素信号 IRS-1/Akt 途径。结果表明，SIT 减弱了胰岛素受体底物-1 丝氨酸磷酸化（p-IRS-1）（P=0.0003）。然而，它上调了 IR（P=0.0036）和受体后胰岛素信号分子的 mRNA 表达，如 IRS-1（P<0.0001）、β-arrestin-2（P<0.0058）、Akt（P=0.0008）、AS160（P=0.0030）和 GLUT4（P<0.0001），同时 IRS-1（P<0.0001）、p-IRS1-1（P=0.0014）、Akt（P<0.0001）、p-Akt（P=0.0006；P<0.0001）、AS160 和 p-AS160（P<0.0001）的水平也随之升高与 2 型糖尿病大鼠相比。还进行了计算机模拟分析，结果表明 SIT 与β-arrestin-2、c-Src 和 IRS-1 以及 Akt 蛋白具有更高的结合亲和力，并证明可减轻胰岛素抵抗，因为这项研究与体内发现相符。我们的研究结果表明，SIT 可减轻高脂肪饮食引起的脂肪组织不良变化。因此，从目前的研究结果可以得出结论，SIT 可作为治疗 2 型糖尿病的潜在植物药。
