PTEN and hyperhomocysteinemia: Although IPC-induced cardioprotection has been documented, the experimental data clearly suggest critical abrogation of the beneficial effects of IPC in metabolic dysregulation caused by hyperhomocysteinemia, probably due to reduced release of calcitonin gene-related peptide (CGRP), the over-expression of glycogen synthase kinase-3β (GSK-3β) and phosphatase and tensin homolog (PTEN), impairment of mito-KATP channels, the consequent opening of mitochondrial permeability transition pore (MPTP) protein kinase C delta, and other mechanisms (Rana et al., 2015).