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目的研究荷叶碱对饮食诱导的胰岛素抵抗小鼠模型的干预作用及其机制。方法以高脂饮食诱导24周的胰岛素抵抗小鼠为模型,分析荷叶碱对肥胖、血糖、胰岛素及稳态模型评估胰岛素抵抗(HOMA-IR)指数的影响,同时探讨其改善胰岛素抵抗的机制。结果经过24周的高脂饮食,模型小鼠形成了明显胰岛素抵抗:肥胖(t=8.1274,P<0.01)、高血糖(P<0.05)、高胰岛素血症及HOMA-IR指数(t=10.215 4,P<0.01;t=7.2897,P<0.01)。荷叶碱有效降低了体重(t=3.750 9,P<0.01)及高糖血症(t=5.236 9,P<0.01)。血清胰岛素水平及HOMA-IR指数也分别降低了60.2%和66.8%(t=6.870 3,P<0.01;t=5.185 6,P<0.01)。荷叶碱通过上调肝组织中IR、IRS1、Glut2及Glut4 m RNA表达改善了糖代谢、提高了胰岛素敏感性(P<0.05),但对IRS2影响不大(t=0.6261,P>0.05)。结论荷叶碱降低了肥胖、高血糖及高胰岛素血症,缓解了胰岛素抵抗,这一作用可能与调控胰岛素信号通路、活化葡萄糖转运信号通路有关。
Objective To study the effects of nuciferine on diet-induced insulin resistance in mice and its mechanism. Methods The 24-week insulin resistance mice induced by high-fat diet were used as models to analyze the effects of nuciferine on the assessment of insulin resistance (HOMA-IR) index in obese, hyperglycemic, insulin and homeostatic models and to explore the mechanism of insulin resistance . Results After 24 weeks of high fat diet, the model mice developed obvious insulin resistance: obesity (t = 8.1274, P <0.01), hyperglycemia (P <0.05), hyperinsulinemia and HOMA-IR index 4, P <0.01; t = 7.2897, P <0.01). Nuciferine effectively reduced body weight (t = 3.750 9, P <0.01) and hyperglycemia (t = 5.236 9, P <0.01). Serum insulin levels and HOMA-IR index decreased by 60.2% and 66.8%, respectively (t = 6.870 3, P <0.01; t = 5.185 6, P <0.01). Norepinefine improved glucose metabolism and increased insulin sensitivity (P <0.05) by up-regulating the expression of IR, IRS1, Glut2 and Glut4 mRNA in liver tissue, but had little effect on IRS2 (t = 0.6261, P> 0.05). Conclusion The decoction reduces the obesity, hyperglycemia and hyperinsulinemia and relieves the insulin resistance. This effect may be related to the regulation of insulin signaling pathway and activation of glucose transport signaling pathway.