Activation of insulin receptor family members results in activation of protein kinase B (PKB, also known as Akt). (i) PKB/Akt signalling influences cell death by reducing mitochondrial-dependent apoptosis, increasing hexokinase II (HKII) and inhibiting glycogen synthase kinase 3 (GSK3) activities. This prevents opening of the mitochondrial permeability transition pore (mPTP). Inhibition of FoxO transcription factors reduces expression of pro-apoptotic proteins. Signalling via mTORC1 inhibits autophagy via Ulk1. Activation of eNOS may reduce cell death, acting to promote vasodilation and, thus, reduce workload. It also reduces vascular inflammation. Phosphorylation of cGAS and STING inhibits interferon production. Increased flux through the pentose phosphate pathway (PPP) increases antioxidant capacity in the cell by increasing production of NADPH and glutathione (GSH). (ii) PKB/Akt increases metabolism, providing the cell with options for reducing oxygen needs whilst sustaining energy production, and maintaining antioxidant capability via the NADPH/glutathione system. Glucose uptake is increased by translocation of GLUT4 to the membrane. HKII increases availability of glucose 6-phosphate (G6P) for both glycolysis and the pentose phosphate pathway (PPP). Phosphorylation of the cardiac isoform of phosphofructokinase 2 (PFKB2) inhibits the phosphatase activity, increasing production of fructose 2,6-bisphosphate, an allosteric activator of glycolysis. Glycogen storage is increased by GSK3 inhibition, providing a source of glucose during ischaemia. FoxO inhibition increases glucose metabolism.