Fig. 8: Model of renal NEDD4-2 loss in db/db.
From: Nedd4-2 ablation in kidney improves glycaemic control in diabetic mice
In diabetic db/db mice, lack of insulin signalling results in hyperglycaemia, subsequent glycosuria, loss of urinary Na+ (increased Na+ excretion) and increased aldosterone levels. Elevated aldosterone can further inhibit insulin signalling. Loss of renal NEDD4-2 results in elevated levels of ENaC and NCC (reported previously, and in this study) to increase Na+ reabsorption. High Na+ can inhibit aldosterone levels to restore insulin signalling, allowing cellular glucose uptake and restoring BGL to normal levels.
