Journal Article

Aldosterone-mediated apical targeting of ENaC subunits is blunted in rats with streptozotocin-induced diabetes mellitus

Heidi O’Neill, Janne Lebeck, Patrick B. Collins, Tae-Hwan Kwon, Jørgen Frøkiær and Søren Nielsen

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 5, pages 1546-1555
Published in print May 2008 | ISSN: 0931-0509
Published online November 2007 | e-ISSN: 1460-2385 | DOI:
Aldosterone-mediated apical targeting of ENaC subunits is blunted in rats with streptozotocin-induced diabetes mellitus

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Background. Diabetes mellitus (DM) is associated with a significant polyuria and natriuesis as well as increased plasma aldosterone and anti-diuretic hormone arginine vasopressin (AVP). This study aimed to determine whether diabetic kidneys compensate for the urinary sodium and water losses by increasing apical targeting of epithelial sodium channel (ENaC) subunits and aquaporin-2 (AQP2) in the collecting duct, in addition to the previously observed changes in ENaC subunit protein expression in different kidney zones.

Methods. Female rats were investigated 2 weeks after induction of DM by streptozotocin administration. Kidneys were examined by immunohistochemisty and semiquantitative immunoblotting.

Results. We demonstrated that the protein expression of renal AQP2, Ser-256 phosphorylated AQP2, AQP3, β- and γ-ENaC (but not α-ENaC) increased consistently with an increased AVP response. In contrast, there were no significant changes in the relative apical targeting of β-, γ- and α-ENaC, and the shift in the molecular weight of γ-ENaC from 85 kDa to 70 kDa was not observed despite increased plasma aldosterone levels. These results were supported by changes in the functional data showing increased solute-free water reabsorption, increased fractional excretion of sodium and an unchanged ratio of potassium to sodium in the urine.

Conclusions. The data demonstrate that diabetic kidneys have a reduced sensitivity to the anti-natriuretic action of elevated plasma aldosterone levels with no relative increase in ENaC subunit apical targeting, whereas there is increased expression of β- and γ-ENaC, which alone may play a role in the increased sodium reabsorption in the kidney in DM.

Keywords: aldosterone; aquaporin; diabetes mellitus; ENaC; vasopressin

Journal Article.  5606 words.  Illustrated.

Subjects: Nephrology

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