Metalloproteinase-2 and -9 (MMP-2/9), whose activities are known to be increased in the plasma of type 1 diabetic patients45,46, have the potential for claudin-5 degradation47,48, while caveolae-mediated internalization of claudin-5 can be promoted by the pro-inflammatory cytokine CCL-249. This evidence concerns the gene CLDN5 and type 1 diabetes mellitus.