Increased VEGF expression in VEGFlow and VEGFhigh transgenic β-cells leads to islet hypervascularization. A: Representative Western blot showing higher expression of VEGF in both VEGFhigh and VEGFlow. B: A 2.7- and 17-fold increase in VEGF protein levels were found in islets from 2-month-old VEGFlow and VEGFhigh mice measured by ELISA, wild-type (WT) mice (white bar), transgenic VEGFlow mice (gray bar), and transgenic VEGFhigh mice (black bar). *P < 0.05 transgenic vs. WT (n = 8–15/group). C: Top panel: detection of endothelial cells by CD31 immunostaining. Middle panel: collagen IV (red) and insulin (green) immunohistochemical analysis of VEGFlow and VEGFhigh islets. Bottom panel: FITC-dextran (green) together with insulin (red) immunostaining was used to label functional islet vessels. D: Morphometric analysis revealed an increase in the vessel area in both VEGFlow and VEGFhigh mice (n = 3/group): WT mice (white bar), transgenic VEGFlow mice (gray bar), and transgenic VEGFhigh mice (black bar). Scale bars, 100 µm. *P < 0.05 transgenic vs. WT. (A high-quality digital representation of this figure is available in the online issue.)