目的:探讨槟榔碱对2型糖尿病大鼠肝脏胰岛素抵抗的影响及其机制。方法:采用高果糖饲料饲养Wistar大鼠12周制备2型糖尿病大鼠模型,实验动物随机分为5组(n=8):对照组、模型组、模型+不同浓度的槟榔碱(0,0.5,1,5mg/kg)组。4周后通过检测血糖、血脂、胰岛素、RT-PCR检测肝脏组成型雄甾烷受体(CAR)、孕甾烷x受体(PXR)、糖代谢相关基因:葡萄糖-6-磷酸酶(G6Pase)、磷酸烯醇式丙酮酸羧激酶(PEPCK)和炎症相关因子:白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)mRNA表达,Western blot检测大鼠肝内p-AKT和葡萄糖转运体4(GLUT4)蛋白表达。结果:1,5mg/kg槟榔碱显著降低糖尿病大鼠体重、空腹血糖、空腹胰岛素、血脂和糖代谢相关基因及炎症相关因子mRNA水平,提高CAR、PXR mRNA水平及p-AKT、GLUT4蛋白水平。结论:槟榔碱可能通过提高CAR和PXR的表达,导致肝脏糖代谢关键酶PEPCK、G6Pase基因表达或者炎性因子肿瘤坏死因子-α(TNF-α)、白介素-6(n-6)表达降低,改善2型糖尿病大鼠肝脏胰岛素抵抗。
Objective: To explore the effects of arecohne on hepatic insulin resistance in type 2 diabetes rats and to elucidate its possible mechanism. Methods: Forty five Wistar rats were fed with high fructose diet for 12 weeks to induce type 2 diabetic rat model, rats were randomly divided into 5 groups( n = 8) : control group, model group and model group were treated with different dose (0,0.5, 1,5 mg/kg) of arecoline. After 4 weeks, the fasting blood glucose, blood lipid and insulin level measured , mRNA expression of liver constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), interleukin- 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were detected by reverse transcription polymerase chain reaction (RT-PCR), the protein expression of p-AKT and glucose transporter4 (GLUT4) were detected by Western blot. Results: 1,5 mg/kg arecoline could significantly decrease the level of fasting blood glucose , blood lipid , blood insulin level and liver G6Pase , PEPCK, ID6, TNF-α mRNA level in type 2 diabetes rats. 1,5 mg/kg arecoline also could significantly increase CAR, PXR mRNA level and p-AKT and GLUT4 protein expression. Conclusion: Arecoline improved hepatic insulin resistance in type 2 diabetes rats by increasing the mRNA levels of CAR and PXR leading to the decreased glucose metabolism and inflammation related genes expression.