3.1.1 Activating PI3K/AKT pathway
PI3K/AKT pathway plays an important role in multitudinous physiological functions, and insulin is its main ligand to regulate metabolism. PI3K/AKT pathway participates the cellular metabolism through directly regulating nutrient transporters, metabolic enzymes and transcriptional factors involved in lipid metabolism (Hoxhaj & Manning, 2020). PI3K, AKT, insulin receptor substrate (IRS), glucose transporter 4 (GLUT4) are the key effector molecules of PI3K/AKT pathway in maintaining glucose homeostasis. Also, PI3K/AKT pathway regulates lipid metabolism by mediating the inhibition of insulin on very low-density lipoprotein secretion (Mazibuko-Mbeje et al., 2019; Sharma, Kim & Rhyu, 2015). Presently, it is generally accepted that early growth response protein 1 (EGR-1) is one of the inhibitors of PI3K/AKT pathway (Yu et al., 2011).
Curcumin (Fig 2) is a diketone compound mainly extracted from Zingiberaceae or Araceae plants, such as the rhizomes of Curcuma longa . Li et al. verified that curcumin and its intracorporal degradation products (hexahydrocurcumin, octahydrocurcumin) alleviated IR, oxidative stress, inflammation and endoplasmic reticulum stress (ERS) in high glucose (HG)-induced HepG2 cells by increasing glucose uptake and inhibiting extracellular regulated protein kinases (ERK)/c-Jun N-terminal kinase (JNK) phosphorylation (Li et al., 2020).
Dendrobium officinale polysaccharide (Supporting Information Table S1) ameliorated T2DM and IR in high fat diet (HFD) combined with streptozotocin (STZ)-induced male BALB/c mice via PI3K/AKT-mediated glycogen synthesis and glucose metabolism. In brief, the polysaccharide promoted glycogen synthase kinase-3 beta (GSK-3β), glycogen synthase and GLUT4 expression, increased pyruvate kinase, hexokinase (HK) and phosphoenolpyruvate carboxykinase activity, reduced fasting blood glucose (FBG) and hepatic steatosis (Wang et al., 2018).
Mogroside is a triterpenoid compound extracted from Siraitia grosvenorii . Mogroside III, Mogroside Ⅳ and Mogroside Ⅴ all positively improved glucose metabolism, with Mogroside Ⅴ being the most effective, according to Liu et al (Liu et al., 2019). Mogroside Ⅴ-treated rats exhibited reduced FBG levels, attenuated liver damages and increased insulin sensitivity through modulating PI3K/AKT pathway.