背景:精制-JQ(JQ-R)是来自金芪降糖片三种主要草药成分的精制提取物的混合物:黄连(毛癣科),黄芪(豆科),和忍冬(卷尾花科)。我们先前的研究表明,JQ-R可以降低糖尿病小鼠和胰岛素抵抗小鼠的空腹血糖水平。研究JQ-R对糖尿病前期的降糖作用,对预防或延缓胰岛素抵抗具有实际应用价值。糖耐量受损和临床糖尿病的发展。
方法:使用高脂肪饮食(HFD)诱导的肥胖小鼠模型研究JQ-R的抗糖尿病潜力。用高脂肪饮食喂养C57BL/6J小鼠(HFD-C57小鼠)4个月。HFD-C57小鼠用JQ-R(每天一次胃内给药,持续4周)或二甲双胍(作为阳性对照)治疗,以及JQ-R对体重的影响,血脂,葡萄糖代谢,胰岛素敏感性,监测β细胞功能。
结果:体重,血清胆固醇,在JQ-R或二甲双胍治疗的小鼠中,稳态模型评估比率(胰岛素抵抗指数)显着降低,糖耐量增强,胰岛素反应改善。此外,即使在相对较高的葡萄糖负荷下,JQ-R和二甲双胍都可以激活肝糖原合成。尽管在二甲双胍治疗的小鼠中糖异生被抑制,在JQ-R处理的小鼠中未观察到。类似于二甲双胍,JQ-R还可以提高高血糖钳夹试验中的葡萄糖输注速率(GIR)。JQ-R也显示增加磷酸化AMPKα和磷酸化乙酰辅酶A羧化酶(ACC)的水平,类似于二甲双胍。
结论:JQ-R可通过调节糖脂代谢减轻HFD诱导的胰岛素抵抗,通过激活AMPK信号通路增加胰岛素敏感性,随后改善β细胞功能。因此,JQ-R可以提供治疗与胰岛素抵抗相关的疾病的替代方案。如糖尿病前期和T2DM。
BACKGROUND: Refined-JQ (JQ-R) is a mixture of refined extracts from three major herbal components of JinQi-JiangTang tablet: Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae), and Lonicera japonica (Caprifoliaceae). Our previous studies have indicated that JQ-R could decrease fasting blood glucose levels in diabetic mice and insulin resistance mice. Investigating the hypoglycemic effect of JQ-R on prediabetes has practical application value for preventing or delaying insulin resistance, impaired glucose tolerance and possibly the development of clinical diabetes.
METHODS: The anti-diabetic potential of JQ-R was investigated using a high fat-diet (HFD)-induced obesity mouse model. C57BL/6J mice (HFD-C57 mice) were fed with high-fat diet for 4 months. HFD-C57 mice were treated with either JQ-R (administered intragastrically once daily for 4 weeks) or metformin (as positive control), and the effects of JQ-R on body weight, blood lipids, glucose metabolism, insulin sensitivity, and beta cell function were monitored.
RESULTS: The body weight, serum cholesterol, and the Homeostasis Model Assessment ratio (insulin resistance index) were significantly reduced in JQ-R or metformin-treated mice, and the glucose tolerance was enhanced and insulin response was improved simultaneously. Moreover, both JQ-R and metformin could activate liver glycogen syntheses even under a relatively high glucose loading. Although glyconeogenesis was inhibited in the metformin treated mice, it was not observed in JQ-R treated mice. Similar to metformin, JQ-R could also improve the glucose infusion rate (GIR) in hyperglycemic clamp test. JQ-R was also shown to increase the levels of phosphorylated AMPKα and phosphorylated acetyl CoA carboxylase (ACC), similar to metformin.
CONCLUSIONS: JQ-R could reduce HFD-induced insulin resistance by regulating glucose and lipid metabolism, increasing insulin sensitivity through activating the AMPK signaling pathway, and subsequently improving β cell function. Therefore, JQ-R may offer an alternative in treating disorders associated with insulin resistance, such as prediabetes and T2DM.