AKT1 and Hyperglycemia: Consistent with this, hyperglycemia in mouse SCs cultured in vitro also downregulated BDNF expression by mechanisms related to inhibition of dephosphorylation of the protein kinase B (Akt)/mTOR pathway, DNA methyltransferase 1 overexpression, and DNA hypermethylation of the BDNF promoter[17]; trichostatin A can increase BDNF expression to improve DPN by improving the XBP-1s/ activating transcription factor-6/GRP78 axis in SCs.[18] Nerve growth factor (NGF) plays a key role in nerve regeneration in the peripheral nervous system.