FIGURE 6.

Crosstalk between the hAEC, the endothelial cell (EC) and the islet β cell (IC) within the PIO. hAEC enhances revascularization of the PIO in a direct manner by secreting 1) angiogenic factors and 2) vegf that improve EC viability, function, proliferation and blood vessel formation, and 3) by producing ECM-degrading proteases (MMP-1) that facilitate EC migration and sprouting. Additionally, hAECs secrete EGF that 4) upregulates IC pdx1 expression, leading to higher IC survival and proliferation, as well as 5) glp1-r expression, leading to an up-regulation of glycolytic genes and vegf-a through the mTOR/HIF-1a pathway, resulting in 6) an improved insulin secretion and 7) a better revascularization of the PIO.