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.