Increased renal sodium reabsorption in early-stage diabetes may be driven by higher basal Na-K-ATPase affinity for sodium due to lower Ser-phosphorylation, rather than altered AT1 receptor function.
Altered NKA regulation may drive early diabetic sodium retention; leaves open phosphorylation-targeted therapies pending human validation.
We determined angiotensin II (Ang II) AT(1) receptor function in terms of Na-K-ATPAse (NKA) stimulation in the proximal tubule (PTs) of streptozotocin-induced diabetic rats. Ang II (10 pM) stimulated NKA activity in PTs of control rats but not diabetic rats. The AT(1) receptor expression was similar, but the expression of G-proteins (G(i)alpha2 and G(i)alpha3) in the PTs was decreased in diabetic compared with control rats. Kinetic studies revealed an increase in NKA affinity, low K(0.5,) for Na, with no changes in V(max) of the enzyme in diabetic compared with control rats. Basal Ser-phosphorylation of NKA alpha1-subunit was lower in diabetic compared with control rats. This data suggest that the higher basal NKA affinity for Na, possibly due to lower Ser-phosphorylaion of alpha1-subunit and not the AT(1) receptor function, in the PTs may be responsible for increased renal Na reabsorption associated with early stage of streptozotocin-induced diabetes.
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Siddiqui et al. (2007) studied this question.
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