a. Representative photomicrographs of ischemic muscle sections from pioglitazone+GW9662-treated and from pioglitazone+FP-124-treated diabetic mice stained with antibody directed against VEGF, 7 days after surgery. Positive staining appears in brown. Magnification ×40. b. VEGF, Akt and pAkt expression 7 days after surgery. Representative Western blot and optical density evaluation of VEGF Akt, pAkt and actin protein content in the ischemic legs of control, pioglitazone-treated, pioglitazone+GW9662-treated, STZ-diabetic, pioglitazone+FP-124-treated and GW9662-treated mice. Pioglitazone normalized VEGF expression with enhanced phosphorylation of Akt in ischemic muscle. After pioglitazone administration, even when PPARγ activity was inhibited by GW9662, STZ-diabetic mice showed a normalized expression of VEGF and enhanced levels of p-Akt Ser473 in ischemic limbs compared to those treated with pioglitazone+FP-124 or with GW1929. Selective PPARγ agonist GW1929 or pioglitazone associated with selective Akt inhibitor FP-124 did not normalize VEGF expression in diabetic micevs STZ-diabetic, pioglitazone+FP-124-treated and GW1929-treated mice. p < 0.05.