Xi You-Li, Li Hong-Xia, Chen Chen, Liu Ya-Qun, Lv Hong-Mei, Dong Shi-Qi, Luo Er-Fei, Gu Ming-Bo, Liu Hua
Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China; Department of Pharmacy, Affiliated Drum Tower Hospital of Nanjing University, Nanjing 210008, China.
Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China.
Chin J Nat Med. 2016 Jan;14(1):48-55. doi: 10.3724/SP.J.1009.2016.00048.
Insulin resistance is the pathophysiological basis of many diseases. Overcoming early insulin resistance highly significant in prevention diabetes, non-alcoholic fatty liver, and atherosclerosis. The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice, and exploring the potential molecular mechanisms. Insulin resistance in mice was induced with a high fat diet for 16 weeks. Animals were then treated with three different doses of baicalin (100, 200, and 400 mg·kg(-1)·d(-1)) for 14 weeks. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), insulin tolerance test (ITT), and skeletal muscle lipid deposition were measured. Additionally, the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated. Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance. Moreover, insulin resistance was significantly reversed. Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle. The properties of baicalin were mediated, at least in part, by inhibition of the AMPK/ACC pathway, a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway, a key regulator of Glycogen synthesis. These data suggest that baicalin, at dose up to 400 mg·kg(-1)·d(-1), is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage, through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.
胰岛素抵抗是许多疾病的病理生理基础。克服早期胰岛素抵抗对预防糖尿病、非酒精性脂肪肝和动脉粥样硬化具有重要意义。本研究旨在评估黄芩苷对高脂饮食诱导的小鼠胰岛素抵抗和骨骼肌异位脂肪储存的治疗效果，并探索其潜在的分子机制。用高脂饮食诱导小鼠胰岛素抵抗16周。然后用三种不同剂量的黄芩苷（100、200和400mg·kg⁻¹·d⁻¹）对动物进行14周的治疗。测量空腹血糖、空腹血清胰岛素、葡萄糖耐量试验（GTT）、胰岛素耐量试验（ITT）和骨骼肌脂质沉积。此外，进一步评估骨骼肌中的AMP激活蛋白激酶/乙酰辅酶A羧化酶和蛋白激酶B/糖原合酶激酶3β途径。黄芩苷显著降低空腹血糖和空腹血清胰岛素水平，减轻高脂饮食诱导的葡萄糖耐量和胰岛素耐量。此外，胰岛素抵抗得到显著改善。病理分析显示，黄芩苷剂量依赖性地降低骨骼肌异位脂肪储存的程度。黄芩苷的作用至少部分是通过抑制从头脂肪生成的关键调节因子AMPK/ACC途径和糖原合成的关键调节因子Akt/GSK-3β途径的激活来介导的。这些数据表明，剂量高达400mg·kg⁻¹·d⁻¹的黄芩苷是安全的，并且能够通过调节骨骼肌AMPK/ACC途径和Akt/GSK-3β途径来减轻胰岛素抵抗和骨骼肌异位脂肪储存。
