High glucose up-regulates ENaC and SGK1 expression in HCD-cells

Hills, Claire E. and Bland, Rosemary and Bennett, Jeanette and Ronco, Pierre M. and Squires, Paul E. (2006) High glucose up-regulates ENaC and SGK1 expression in HCD-cells. Cellular Physiology and Biochemistry, 18 (6). pp. 337-346. ISSN 1015-8987

Full content URL: http://dx.doi.org/10.1159/000097611

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Abstract

Background/Aim: Diabetic nephropathy is associated with progressive renal damage, leading to impaired function and end-stage renal failure. Secondary hypertension stems from a deranged ability of cells within the kidney to resolve and appropriately regulate sodium resorption in response to hyperglycaemia. However, the mechanisms by which glucose alters sodium re-uptake have not been fully characterised.

Methods: Here we present RT-PCR, western blot and immunocytochemistry data confirming mRNA and protein expression of the serum and glucocorticoid inducible kinase (SGK1) and the a conducting subunit of the epithelial sodium channel (ENaC) in a model in vitro system of the human cortical collecting duct (HCD). We examined changes in expression of these elements in response to glucose challenge, designed to mimic hyperglycaemia associated with type 2 diabetes mellitus. Changes in Na+ concentration were assessed using single-cell microfluorimetry.

Results: Incubation with glucose, the Ca2+-ionophore ionomycin and the cytokine TGF-beta 1 were all found to evoke significant and time-dependent increases in both SGK1 and alpha ENaC protein expression. These molecular changes were correlated to an increase in Na+-uptake at the single-cell level.

Conclusion: Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy.

Keywords:Glucose
Subjects:Library of Congress Subject Areas > Q Science > QH Natural history > QH301 Biology
Library of Congress Subject Areas > Q Science > QP Physiology
Divisions:College of Science > School of Life Sciences
ID Code:14084
Deposited On:20 Apr 2011 16:17

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