College of Food Science, Southwest University, 2 Tiansheng Road, Beibei, Chongqing 400715, PR China.
Food Funct. 2021 Apr 21;12(8):3740-3753. doi: 10.1039/d0fo02695f. Epub 2021 Apr 7.
Type 2 diabetes mellitus (T2DM) can easily induce insulin resistance (IR) in skeletal muscle, causing protein metabolism disorder and inflammation. The present study aimed to investigate whether Zanthoxylum alkylamides (ZA) could ameliorate T2DM through regulating protein metabolism disorder by using a rat model of T2DM. The predominant bioactive constituents found in ZA were hydroxyl-α-sanshool, hydroxyl-β-sanshool and hydroxyl-γ-sanshool. The results showed that ZA improved a series of biochemical indices associated with protein metabolism and inflammation in T2DM rats. Our mechanistic finding indicated that ZA promoted protein anabolism in T2DM rats by up-regulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. ZA also promoted glucose transportation in skeletal muscle to ameliorate skeletal muscle IR and energy metabolism through regulating the AMP-activated protein kinase (AMPK) signaling pathway. Moreover, ZA inhibited protein degradation and improved protein catabolism disorder in T2DM rats by down-regulating the PI3K/Akt/forkhead box O (FoxO) signaling pathway, and ZA further ameliorated inflammation to inhibit protein catabolism via regulating the tumor necrosis factor α (TNF-α)/nuclear factor κB (NF-κB) pathway in the skeletal muscle of T2DM rats. Collectively, the ameliorating effect of ZA on protein metabolism disorder in T2DM rats was the common result of regulating multiple signaling pathways. ZA decreased skeletal muscle IR to promote protein anabolism and inhibit protein catabolism for improving protein metabolism disorder, thus ultimately ameliorating T2DM. In sum, our findings demonstrated that ZA treatment could effectively ameliorate T2DM through improving protein metabolism, providing a new treatment target for T2DM.
2 型糖尿病（T2DM）可使骨骼肌易发生胰岛素抵抗（IR），导致蛋白质代谢紊乱和炎症。本研究旨在通过使用 T2DM 大鼠模型，探讨花椒酰胺（ZA）是否可以通过调节蛋白质代谢紊乱来改善 T2DM。ZA 中发现的主要生物活性成分是羟基-α-花椒素、羟基-β-花椒素和羟基-γ-花椒素。结果表明，ZA 改善了 T2DM 大鼠与蛋白质代谢和炎症相关的一系列生化指标。我们的机制研究结果表明，ZA 通过上调磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路促进 T2DM 大鼠的蛋白质合成。ZA 还通过调节 AMP 激活的蛋白激酶（AMPK）信号通路促进骨骼肌中的葡萄糖转运，以改善骨骼肌 IR 和能量代谢。此外，ZA 通过下调 PI3K/Akt/叉头框 O（FoxO）信号通路抑制 T2DM 大鼠蛋白质降解并改善蛋白质分解代谢紊乱，ZA 还通过调节肿瘤坏死因子 α（TNF-α）/核因子 κB（NF-κB）通路进一步改善炎症，抑制 T2DM 大鼠骨骼肌中的蛋白质分解代谢。总之，ZA 改善 T2DM 大鼠蛋白质代谢紊乱的作用是调节多种信号通路的共同结果。ZA 降低骨骼肌 IR 以促进蛋白质合成并抑制蛋白质分解代谢，从而改善蛋白质代谢紊乱，最终改善 T2DM。总之，我们的研究结果表明，ZA 治疗可有效改善 T2DM，改善蛋白质代谢，为 T2DM 提供了新的治疗靶点。
