Inhibition of VEGFR-2 Reverses Type 1 Diabetes in NOD Mice by Abrogating Insulitis and Restoring Islet Function

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FIG. 5.
FIG. 5.

VEGFR-2 inhibition reduces insulitis and preserves islet function. AD: Representative micrographs of new-onset pancreata used to score the severity of insulitis in VEGFR-2 antagonists and control (MC) mice. The red line in A depicts the approximated islet boundary. The red arrow in D highlights an islet with severe insulitis. Black arrows highlight islets without insulitis. E: Quantification of the severity of insulitis reported as the percentage of islets with a given disease score. The number within each bar represents the levels of significance determined by Student t test (the indicated value = P value). At least 100 islets were scored per mouse. Five to ten mice per group were analyzed. F: Measurement of the expression levels of T-cell activation markers by flow cytometry reveals no differential expression between MC and PF-337210 (PF)–treated prediabetic mice. uns, unstimulated. G: Glucose tolerance tests reveal that 14-week-old, prediabetic mice that were treated with PF (10 mg/kg) for 3 weeks had improved glucose tolerance relative to MC-treated mice. Five mice per group were used. #P < 0.0001; *P < 0.01, PF-treated relative to MC-treated mice. H: Quantification of area under the curve shows a significant decrease in PF-treated mice, but levels were still higher than 4-week-old NOD females. ♦P < 0.05, relative to 4-week NOD; *P < 0.05, relative to MC. IK: Diabetic mice were treated daily for 3 days with PF (10 mg/kg) or MC. The red line in I indicates a blood glucose value of 250 mg/dL. A 3-day treatment significantly reduced blood glucose levels (I), retained insulin content (J), and did not significantly affect serum insulin levels (K) in PF-treated mice. ♦P < 0.05, relative to new-onset mice (NO). L: The insulin response after a fasting IPGTT in prediabetic NOD mice treated for 3 weeks with PF (10 mg/kg) or MC.

This Article

  1. Diabetes vol. 62 no. 8 2870-2878