Figure 2: Proposed Schema for GLP-1 Activation of Ischemic Conditioning Pathways

GLP-1 binds to the GLP-1 receptor and activates the PI3K-Akt complex, which is part of the RISK pathway. This complex activates a cascade that opens the mK-ATP channel. Opening of mK-ATP prevents opening of the mPTP during reperfusion, part of the final common pathway of cell death. Activation of PI3-Akt has also been associated with changes in transcription and translation promoting cell survival. Alternative receptors, or activation of pro-survival pathways without binding the GLP-1 receptor, may explain myocardial cardioprotection, despite the purported absence of the GLP-1 receptor in recent studies. GLP-1R = GLP-1 receptor; GLP-1RA = GLP-1 receptor agonist; mPTP = mitochondrial permeability transition pore.