Altered sodium metabolism is a consistent finding in diabetes, and it is present even in the absence of overt renal or cardiac disease. Both insulin-dependent and non-insulin-dependent diabetic individuals have been reported to have a significant increase of total exchangeable sodium relative to non-diabetic controls (O'hare et al., 1985; Bickel et al., 2002). In cultured cells, AMPK was shown to regulate renal epithelial currents mediated by ENaC (Bhalla et al., 2006), ROMK (Siraskar et al., 2013), and CFTR (Takiar et al., 2011). Analysis of renal function in mice with genetic deletion of the AMPK α1 catalytic subunit showed normal renal sodium handling and a moderate antidiuretic state that might indicate a compensatory upregulation in α2 subunit. A renal epithelium-specific knock down of α2 subunit in the α1 knockout strain was accompanied by reduced renal AMPK activity and a moderate salt/water wasting phenotype on normal and high salt diets (Lazo-Fernández et al., 2017).