PRRT2 and Insulin resistance: Specifically, hyperglycemia, dyslipidemia, and insulin resistance synergistically activate the protein kinase C (PKC), polyol, hexosamine, advanced glycation end products (AGEs)/receptor for AGEs (RAGE) signaling cascades, which collectively induce inflammation, oxidative stress, mitochondrial dysfunction, and culminate in neuronal apoptosis (30, 32).