Figure 2.

Opposing effects of CB₁ receptor and CB₂ receptor in DN. The CB₁ receptor has deleterious pro‐oxidative and pro‐inflammatory effects, while opposing protective effects are induced by CB₂ receptor activation. In diabetes, hyperglycaemia and hypertension alter the balance between CB₁ receptor and CB₂ receptor signalling as CB₁ receptor expression is enhanced, while CB₂ receptor is down‐regulated. This imbalance favours oxidative stress, inflammatory and profibrotic processes and contributes to the development of proteinuria by enhancing nephrin loss and of renal function loss by exacerbating fibrogenesis in both the mesangium and tubulointerstitium.