FIG. 5.

Glucose homeostasis in VEGF^low and VEGF^high mice was impaired with age. Glucose tolerance (A) and insulin in vivo secretion (B) were measured in 12-month-old wild-type (WT) (white circle) and VEGF^low mice (gray square) (n = 12 animals/group). *P < 0.05 VEGF^low vs. WT mice. Glucose tolerance (C) was determined in parallel to in vivo insulin secretion (D) after a glucose load (2 g/kg body weight [b.w.]) in 5-month-old WT mice (white circle) and transgenic VEGF^high mice (black square). At this age, VEGF^high mice were normoglycemic, but showed impaired insulin release and glucose intolerance after the glucose load (n = 12 animals/group). *P < 0.05 VEGF^high vs. WT mice. E: Eight-month-old VEGF^high mice (black square) were glucose-intolerant compared with age-matched WT (white square) mice as shown by a glucose tolerance test (1 g/kg b.w.) (n = 10 animals/group). *P < 0.05 VEGF^high vs. WT mice. F: Top panel: representative images of insulin immunostaining of islets. Middle panel: immunohistochemical analysis of insulin (green) and glucagon (red) expression. Bottom panel: immunohistochemical analysis of collagen IV (red) and insulin (green). Islets from 12-month-old WT and VEGF^low and 8-month-old VEGF^high mice are shown. Scale bars, 100 µm. G: β-Cell mass was determined by insulin immunostaining in 8- and 12-month-old VEGF^low and 8-month-old VEGF^high mice and compared with age-matched WT mice, as indicated in Research Design and Methods (WT mice [white bar], transgenic VEGF^low mice [gray bar], and transgenic VEGF^high mice [black bar]) (n = 3 sections/mouse and 4 animals/group). **P < 0.001 VEGF^high vs. WT mice, ^#P < 0.1 VEGF^low vs. WT. (A high-quality digital representation of this figure is available in the online issue.)