Fig. 1

Validation of the model: FGF-2 binding, hyperglycemia and rising albumin/creatinine ratio (ACR). Binding of exogenous FGF-2 (in red fluorescence) with endothelial HS was reduced in the Ndst1f/fTie2Cre+ animals compared to the Ndst1f/fTie2Cre− mice (a, b) indicating reduced N-sulfation and 2-O-sulfation of HS. After administrating streptozotocin for 5 consecutive days plasma glucose starts to rise from baseline, reaching approximately 500 mg/dl at 6 weeks after the diabetes induction (c). No differences in blood glucose levels were observed between Ndst1f/fTie2Cre− and Ndst1f/fTie2Cre+ diabetic animals. The urinary albumin/creatinine ratio (ACR) starts to increase after induction of diabetes reaching significant level at 6 weeks (WT:p < 0.05 and KO: p < 0.01), showing albuminuria is developing. No significant difference in ACR, both at 2 and 6 weeks post diabetes induction, was seen between the Ndst1f/fTie2Cre− and Ndst1f/fTie2Cre+ group. In healthy control Ndst1f/fTie2Cre+ animals, no albuminuria is developing (d).