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Am J Physiol Renal Physiol (August 5, 2003). doi:10.1152/ajprenal.00143.2003
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Submitted on April 9, 2003
Accepted on August 4, 2003

Increased Renal ENaC Subunit and Sodium Transporter Abundances in Streptozotocin-Induced Type I Diabetic Rats

Jian Song1, Mark A. Knepper2, Joseph G. Verbalis1, and Carolyn A. Ecelbarger1*

1 Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University, Washington, DC, USA
2 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

* To whom correspondence should be addressed. E-mail: ecelbarc{at}georgetown.edu.

Uncontrolled diabetes mellitus (DM) is associated with copious water and sodium losses. We hypothesized that the kidney compensates for these losses by increasing the abundances of key sodium and water transporters and channels. Using targeted proteomic analysis via immunoblotting of kidney homogenates, we examined comprehensive regulation of transport proteins. In three studies, streptozotocin- STZ (65 mg/kg) or vehicle was administered intraperitoneally to male, Sprague-Dawley rats. In study 2, to control for potential renal toxicity of STZ, one group of STZ-treated rats was intensively treated with insulin to control diabetes. In another group, the reversibility of DM and related changes was assessed, by treating with insulin for the final 4 days. In Study 3, we correlated blood glucose to transporter changes by treating with different doses of insulin. In Study 1, STZ treatment resulted in significantly increased band densities for: the sodium hydrogen exchanger (NHE3), the thiazide-sensitive Na-Cl cotransporter (NCC), the epithelial sodium channel (ENaC) subunits ({alpha}, {beta}, and {gamma}- (85-, and 70-kDa bands) to (% vehicle mean): 204, 125, 176, 132, 147, 241, respectively. In Study 2, aquaporins (AQPs) 2 and 3 were increased with DM, but not AQP1 or AQP4. Neither these changes, nor blood glucose itself, could be returned to normal by short-term intensive insulin treatment. Whole kidney abundance of AQP3, NKCC2 (the bumetanide-sensitive Na-K-2Cl cotransporter), and {gamma}-ENaC (85-kDa band) correlated most strongly with blood glucose, in Study 3. These comprehensive changes would be expected to decrease volume contraction accompanying large solute and water losses associated with DM.




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