REN and Hyperglycemia: In STZ-diabetic rats, disruption to GFB integrity is expected to start within 2 months of hyperglycemia due to high glucose as such (via e.g., advanced glycation end products), inflammatory cytokines, reactive oxygen species, activation of the renin–angiotensin system, systemic endothelial dysfunction, and loss of podocytes and their function (Barton 2008; Yuen et al.