Phosphorylation of GSK3 β not only activates target enzymes of the insulin-signaling pathway [ 20] but also regulates hepatic glycogen synthesis by increasing glycogen synthase (GS) expression.
Here it activates target genes, one of which is the suppressor of cytokine signaling 1 (SOCS1), an important mediator of negative feedback.
In mammalian systems PA is reported to activate target of rapamycin (mTOR) kinase resulting in elevated levels of 4EBP and phosphorylated S6K (Fang et al., 2001).
In addition to its nutritive properties, leucine has signaling properties, activating mammalian target of rapamycin (mTOR) and the 70-kDa ribosomal S6 kinase (p70S6 K), both of which alter insulin signaling.
Rheb in its active form activates mammalian target of rapamycin complex 1 (mTORC1), a key regulator of protein translation, metabolism and cell proliferation.
Acute hyperglycemia activated mechanistic target of rapamycine (mTOR) pathway, as it significantly increased the phosphorylation of mTOR and S6 proteins and the phosphorylation of AKT.
In a separate study, cystatin C upregulation activated mammalian target of rapamycin (mTOR -dependent autophagy while pharmTOR -dependent of autophagy prevented the cystatin C-induced protein clearance [ 50].
As we will discuss later, insulin therapy may accelerate complications because insulin and insulin-like growth factor 1 (IGF-1) activate mammalian target of rapamycin (mTOR).
However, unexpectedly, DC120 activated mammalian target of rapamycin complex 1 (mTORC1) pathway that was suggested by increased phosphorylation of 70KD ribosomal protein S6 kinase (P70S6K) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1).
AA activated mammalian target of rapamycin complex 2 (mTORC2) and Aktser473 through the GPR40/phosphoinositide 3-kinase (PI3K) signaling, which was responsible for the stimulation of an atypical protein kinase C (PKC) isoform, PKC ζ.
