Figure 4.

Schematic for epithelial Na⁺ channel (ENaC) induced tubular renal injury in DKD. Hyperglycemia and hyperinsulinemia induced via diabetes cause over-activation of the renin-angiotensin-aldosterone system (RAAS), long-term oxidative stress, and serum and glucocorticoid-regulated kinase (SGK) 1 activation that all directly cause the increase in the ENaC activation and/or expression. This increase in ENaC leads to various factors shown in the above pathway, such as hypertension. The culmination of these factors result in the development of the major characteristics of DKD.