Department of Nutrition, China Medical University, Taichung, Taiwan.
Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan.
Am J Chin Med. 2020;48(5):1073-1090. doi: 10.1142/S0192415X20500524.
Pro-inflammatory cytokines interfere with blood glucose homeostasis, which leads to hyperglycemia. (AP) has been shown to possess anti-inflammatory activity and to reduce blood glucose levels in diabetes. The two major bioactive diterpenoids in AP, andrographolide (AND) and 14-deoxy-11,12-didehydroandrographolide (deAND), have potent anti-inflammatory activity. We studied whether APE (an ethanolic extract of AP), AND, and deAND could improve a high-fat diet (HFD)-induced hyperglycemia and TNF[Formula: see text]-induced impairment of insulin signaling . Male C57BL/6JNarl mice were fed a normal diet (ND) or the HFD, and the fatty mice were treated with APE, deAND, or AND for 16 weeks. 3T3-L1 cells were used to study the underlying mechanisms by which APE, deAND, or AND attenuated TNF[Formula: see text]-induced insulin resistance. The HFD significantly induced obesity, hyperglycemia, insulin resistance, and inflammation, whereas APE and deAND significantly ameliorated HFD-induced obesity, hyperglycemia, insulin resistance, and TNF[Formula: see text] production. The HFD significantly impaired insulin signaling by decreasing the protein expression of p-IRS1 tyr632 and p-AKT ser473, as well as the membrane translocation of GLUT4 in response to insulin stimulation in epididymal adipose tissue. HFD-impaired the membrane translocation of GLUT4 was significantly reversed by deAND and APE. In addition, deAND and APE markedly reversed the detrimental effect of TNF[Formula: see text] on the insulin signaling pathway and glucose uptake in 3T3-L1 cells. Despite no significant positive effect on p-AS160, a trend for recovery by deAND and APE was observed. These results suggest that deAND and APE protect against HFD-induced insulin resistance by ameliorating inflammation-driven impairment of insulin sensitivity.
促炎细胞因子干扰血糖稳态，导致高血糖。穿心莲内酯（AP）已被证明具有抗炎活性，并能降低糖尿病患者的血糖水平。AP 中的两种主要生物活性二萜，穿心莲内酯（AND）和 14-脱氧-11,12-二去氢穿心莲内酯（deAND），具有很强的抗炎活性。我们研究了 AP 的乙醇提取物（APE）、AND 和 deAND 是否能改善高脂肪饮食（HFD）诱导的高血糖和 TNF[Formula: see text]诱导的胰岛素信号受损。雄性 C57BL/6JNarl 小鼠分别喂食正常饮食（ND）或 HFD，并用 APE、deAND 或 AND 治疗 16 周。3T3-L1 细胞用于研究 APE、deAND 或 AND 减弱 TNF[Formula: see text]诱导的胰岛素抵抗的潜在机制。HFD 显著诱导肥胖、高血糖、胰岛素抵抗和炎症，而 APE 和 deAND 显著改善 HFD 诱导的肥胖、高血糖、胰岛素抵抗和 TNF[Formula: see text]的产生。HFD 通过降低胰岛素刺激后附睾脂肪组织中 p-IRS1 tyr632 和 p-AKT ser473 的蛋白表达以及 GLUT4 的膜转位，显著损害胰岛素信号。deAND 和 APE 显著逆转了 HFD 对 GLUT4 膜转位的损害。此外，deAND 和 APE 显著逆转了 TNF[Formula: see text]对 3T3-L1 细胞胰岛素信号通路和葡萄糖摄取的不良影响。尽管 deAND 和 APE 对 p-AS160 没有明显的正向作用，但观察到恢复的趋势。这些结果表明，deAND 和 APE 通过改善炎症驱动的胰岛素敏感性损害来防止 HFD 诱导的胰岛素抵抗。
