Fig. 1.

Diabetes and prolonged exposure to high glucose impair hypoxic induction of VEGF expression. Cells were placed in hypoxia (0.5% O₂) or normoxia (21% O₂), and levels of VEGF secretion were measured by ELISA. (A) Dermal fibroblasts isolated from diabetic patients produced less VEGF. (B) Fibroblasts from normal human foreskins were cultured chronically (4 weeks) in low glucose (LG) or high glucose (HG). VEGF protein expression was significantly attenuated in cells grown in HG and exposed to hypoxia. (C) Schematic depicting murine ischemic model used. Tissue oxygen tensions are highest in the most proximal (cranial) part of the tissue bed [A] and decrease in a gradient to the most distal (caudal) part [C]. (D) VEGF levels in ischemic skin segments of normal mice measured 24 and 72 h after ischemic induction. (E) VEGF protein levels in ischemic skin tissue from db/db mice. All values represent mean ± SEM. *, P < 0.05 vs. baseline. ‡, P < 0.05 vs. zone A. ¶, P < 0.05 vs. 24 h. n = 6 for all panels. Nl, normal skin.