Ramalingam Sundaram, Packirisamy Meenatchi, Karuppiah Muthu, Vasu Ganesh, Gopalakrishnan Rahul, Gothandam Kirubananthan, Thiruppathi Muthusamy
Central Research Laboratory, Meenakshi Academy of Higher Education and Research, West K.K. Nagar, Chennai, Tamil Nadu, India.
Department of Biochemistry, Saveetha Dental College & Hospital, Saveetha Institute of Medical & Technical Sciences, Vellapanchavadi, Chennai, Tamil Nadu, 600077, India.
Cytotechnology. 2020 Jun;72(3):357-366. doi: 10.1007/s10616-020-00382-y. Epub 2020 Mar 2.
β-Sitosterol is a plant derived compound similar to cholesterol structure and used in the treatment of hypercholesterolemia, prostate cancer, breast cancer and coronary artery disease. But no studies have been reported the effect of β-sitosterol on glucose homeostasis by sensitization of insulin resistance via enhanced protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and glucose transporter 4 (GLUT4) in insulin dependent tissues of high fat diet and streptozotocin-induced diabetic rats.
Type 2 diabetes was induced in male albino Wistar rats by feeding them with high fat diet comprising of 84.3% standard laboratory chow, 5% lard, 10% yolk powder, 0.2% cholesterol and 0.5% bile salt for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (35 mg/kg, dissolved in 0.1 M sodium citrate buffer, pH 4.5). Analysis of blood glucose, insulin, hemoglobin and glycated hemoglobin were done by commercially available diagnostic kits. The PPARγ and GLUT4 were analyzed by western blotting using respective primary and secondary antibodies.
Upon administration of β-sitosterol at a dose of 15 mg/kg body weight per day to high fat diet and streptozotocin induced diabetic rats for 30 days significantly decreased the levels of plasma glucose, homeostatic model assessment of insulin resistance and glycosylated hemoglobin and increased the levels of insulin, hemoglobin and protein expression of PPARγ and GLUT4 in insulin dependent tissues. Furthermore, β-sitosterol administration prevented the body weight loss and excessive intake of food and water.
These finding suggest that β-sitosterol can replace the commercial drugs which could lead to reduction in toxicity and side effect caused by the later as well as reduce the secondary complications.
β-谷甾醇是一种植物衍生化合物，其结构与胆固醇相似，用于治疗高胆固醇血症、前列腺癌、乳腺癌和冠状动脉疾病。但尚无研究报道β-谷甾醇通过增强过氧化物酶体增殖物激活受体γ（PPARγ）和葡萄糖转运蛋白4（GLUT4）在高脂饮食和链脲佐菌素诱导的糖尿病大鼠胰岛素依赖组织中的蛋白表达来改善胰岛素抵抗，从而对葡萄糖稳态产生影响。
通过给雄性白化Wistar大鼠喂食由84.3%标准实验室饲料、5%猪油、10%蛋黄粉、0.2%胆固醇和0.5%胆盐组成的高脂饮食2周来诱导2型糖尿病。2周后，动物禁食过夜并注射低剂量链脲佐菌素（35mg/kg，溶解于0.1M柠檬酸钠缓冲液，pH4.5）。使用市售诊断试剂盒进行血糖、胰岛素、血红蛋白和糖化血红蛋白的分析。通过使用各自的一抗和二抗进行蛋白质印迹分析PPARγ和GLUT4。
对高脂饮食和链脲佐菌素诱导的糖尿病大鼠每天给予剂量为15mg/kg体重的β-谷甾醇30天，可显著降低血浆葡萄糖水平、胰岛素抵抗的稳态模型评估值和糖化血红蛋白水平，并提高胰岛素、血红蛋白水平以及胰岛素依赖组织中PPARγ和GLUT4的蛋白表达。此外，给予β-谷甾醇可防止体重减轻以及食物和水的过量摄入。
这些发现表明，β-谷甾醇可以替代商业药物，这可能会降低后者引起的毒性和副作用，并减少继发性并发症。
