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胰岛素抵抗(IR)是导致2型糖尿病和多种代谢性疾病发生发展的共同病理生理基础,通过模拟能量限制调控能量代谢网络已经成为防治IR相关疾病的研究热点.本课题组前期研究结果提示,中药复方糖耐康可能通过激活SIRT1-AMPK通路模拟能量限制效应改善IR.通过比较糖耐康和能量限制对自发性2型糖尿病db/db小鼠(Mus musculus)糖脂代谢、胰岛功能、线粒体功能和胰岛素敏感性的影响,进一步验证糖耐康是否可在整体和分子水平模拟能量限制效应进而干预IR.与对照组相比,糖耐康和能量限制均可相似地显著改善db/db小鼠口服葡萄糖耐量(OGTT)、降低空腹血胰岛素(FINS),升高胰岛素敏感指数(ISI).同时糖耐康和能量限制还可相似地升高糖负荷后30 min胰岛素分泌与血糖变化比值(?I30/?G30),降低肌肉TG含量,上调肌肉组织AMPK磷酸化水平以及SIRT1和PGC1?的蛋白表达水平,不同程度提高肌肉组织线粒体质量和数量.以上结果表明,糖耐康可显著改善db/db小鼠的糖代谢、胰岛功能、脂质异位沉积、线粒体功能和IR,激活肌组织AMPK/SIRT1/PGC1?信号通路,上调肌肉脂肪酸氧化相关基因表达,在整体效应和能量代谢转录调控方面具有能量限制拟似效应,进而从新的视角揭示了糖耐康干预IR的药效模式和分子机制.
Insulin resistance (IR) is the common pathophysiological basis for the development of type 2 diabetes mellitus and many metabolic diseases, and the energy metabolism network has become a research hotspot in the prevention and treatment of IR-related diseases through the simulation of energy restriction.Preliminary results of this research group suggest that, The traditional Chinese medicine Tangnan Kang may improve the IR by simulating the energy-limited effect of activating SIRT1-AMPK pathway.Through the comparison of glucose tolerance and energy limitation on the glucose metabolism, islet function, mitochondria of spontaneous type 2 diabetes db / db mice (Mus musculus) Function and insulin sensitivity to further validate whether glucose-resistant Kang can simulate the energy-limiting effect at the whole and molecular levels and then interfere with IR.Compared with the control group, glucose and Kang Qikang and energy constraints can be significantly improved db / db small The oral glucose tolerance (OGTT), fasting blood insulin (FINS) and insulin sensitivity index (ISI) were increased in the rats, and the glucose tolerance and energy limitation also increased the ratio of insulin secretion to blood glucose at 30 min ? I30 /? G30), reduce muscle TG content, muscle AMPK phosphorylation and SIRT1 and PGC1? Protein expression levels, to varying degrees, increase muscle The results showed that, Tangkangkang significantly improved glucose metabolism, islet function, lipid deposition, mitochondrial function and IR, and activated AMPK / SIRT1 / PGC1? Signaling pathway in db / db mice , Upregulate the expression of genes related to fatty acid oxidation in muscle, which has the energy-limited quasi-effect on the overall effect and energy metabolism and transcriptional regulation, and then reveals the pharmacodynamic model and molecular mechanism of IRT from a new perspective.