“…Besides changes in expression of STK39/SPAK, it has been observed that STK39/SPAK and its substrate NCC (Na-Cl co-transporter), are highly phosphorylated in hyperinsulinemic db/db mice compared to non-diabetic db/db mice (Nishida et al, 2012), indicating a role for STK39 and NCC in the development of T2DM. In addition, clinical studies with the NCC specific inhibitor, thiazide, used to prevent high blood pressure, showed that patients with diabetes increase their fasting glucose and decrease their insulin sensitivity after administration of thiazide, indeed suggesting that the WNK/SPAK/NCC-pathway is involved in increasing insulin resistance (Eriksson et al, 2008;Hirst et al, 2015). Besides affecting NCC, STK39/SPAK can also inactivate the chloride-transporter CFTR, which is involved in Cystic Fibrosis (Yang et al, 2011).…”