脂代谢：

腺苷酸活化蛋白激酶（AMP activated protein kinase, AMPK）是机体维持体内能量平衡与细胞能量稳态的关键蛋白，是研究糖尿病及其他相关代谢疾病的核心[1]。AMPK可调控下游合成脂肪酸相关的乙酰辅酶Ａ羧化酶1（Acetyl CoA car boxylase, ACC1）和脂肪生成转录因子固醇调控元件结合蛋白1（Sterol regulatory element binding protein, SREBP1）。AMPK发生磷酸化后AMPK/SREBP1通路被激活可抑制SREBP1的活性，增加ACC磷酸化水平，抑制ACC1和脂肪酸合成酶（Fatty acid synthase, FAS）的表达，从而抑制脂肪合成[2,3]。可通过介导AMPK/SREBP1通路减轻糖尿病大鼠体内脂代谢紊乱。

糖代谢：

胰岛素抵抗是T2DM的主要危险因素^[4]。PI3K/AKT信号通路在葡萄糖稳态、胰岛素信号传导过程中起着核心作用。PI3K是一种磷脂酰肌醇激酶，由一个催化亚基（p110）和一个调节亚基（p85）组成，可调控下游糖异生关键酶磷酸烯醇式丙酮酸羧激酶1（phosphoenolpyruvate carboxykinase, PCK1）和糖原合酶激酶-3β（glycogen synthase kinase-3β, GSK-3β）活性，参与调节血糖水平和合成糖原过程^[5,6]。可激活PI3K/AKT信号通路降低PCK1和GSK-3β活性，糖原合酶合成糖原，降低血糖。

[1]          陈金城, 张吟. AMPK与肝脏糖异生研究进展[J]. 中国现代应用药学, 2017, 34(7): 1062–1067. DOI:10.13748/j.cnki.issn1007-7693.2017.07.030

[2]          ZHAO Z, WANG C, ZHANG L, et al. Lactobacillus plantarum NA136 improves the non-alcoholic fatty liver disease by modulating the AMPK/Nrf2 pathway[J]. Applied Microbiology and Biotechnology, 2019, 103(14): 5843–5850. DOI:10.1007/s00253-019-09703-4.

[3]          QUAN H Y, KIM D Y, KIM S J, et al. Betulinic acid alleviates non-alcoholic fatty liver by inhibiting SREBP1 activity via the AMPK-mTOR-SREBP signaling pathway[J]. Biochemical Pharmacology, Elsevier Inc., 2013, 85(9): 1330–1340. DOI:10.1016/j.bcp.2013.02.007.

[4]          GAO Z, ZHANG X, ZUBERI A, et al. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes[J]. Molecular Endocrinology, 2004, 18(8): 2024–2034. DOI:10.1210/me.2003-0383.

[5]          MACAULAY K, WOODGETT J R. Targeting glycogen synthase kinase-3 (GSK-3) in the treatment of Type 2 diabetes[J]. Expert Opinion on Therapeutic Targets, 2008, 12(10): 1265–1274. DOI:10.1517/14728222.12.10.1265.

[6]          LI X, WANG E, YIN B, et al. Effects of lactobacillus casei CCFM419 on insulin resistance and gut microbiota in type 2 diabetic mice[J]. Beneficial Microbes, 2017, 8(3): 421–432. DOI:10.3920/BM2016.0167.