INS and Hyperglycemia: Impaired insulin signaling has been reported to affect the brain in addition to peripheral tissues, as indicated by a decrease in protein kinase B phosphorylation in various animal and cell models of insulin resistance [134], and hyperglycemia can cause alterations in intracerebral insulin signaling pathways by protein glycosylation, which could result in an increase in Aβ deposits and phosphorylation of tau proteins [135].