Adrenalectomy blocks the compensatory increases in UT-A1 and AQP2 in diabetic rat kidney.
In normal rats we showed that glucocorticoids participate in the downregulation of UT-A1 protein abundance in the inner medullary tip and in lowering of basal and vasopressin-stimulated facilitated urea permeability in terminal IMCDs. To examine the relevance of this response to a rat model of human disease, we studied rats with uncontrolled diabetes mellitus (DM) induced by streptozotocin (STZ), since these rats have increased corticosterone production and urea excretion. We found that at 3 days of DM, UT-A1 protein abundance is downregulated in the inner medullary tip compared to pair-fed control rats, while DM for more than 7 days caused an increase in UT-A1. To test whether adrenal steroids could be a mechanism contributing to the latter increase, we studied adrenalectomized rats (ADX), ADX rats given STZ to induce diabetes (ADX + STZ), and ADX + STZ rats receiving exogenous aldosterone or dexamethasone. In contrast to control rats, UT-A1 protein abundance was not increased by prolonged DM in the ADX rats. Aquaporin 2 (AQP2) was not increased in the inner medullas of 10-day DM rats either. However, UT-A1 protein abundance was significantly reduced in the inner medullary tips from both diabetic aldosterone-treated (40 +/- 2%) and dexamethasone-treated (43 +/- 2%) ADX rats compared to diabetic ADX rats without steroid replacement. AQP2 was unaffected by steroid hormone treatments. Thus, both mineralocorticoids and glucocorticoids downregulate UT-A1 protein abundance in rats with uncontrolled diabetes mellitus for 10 days. These results suggest that: 1) the increase in UT-A1 observed in DM is dependent upon having adrenal steroids present; and 2) adrenal steroids are not sufficient to enable the compensatory rise in UT-A1 to a steroid-deficient diabetic animal.
Klein
J D
JD
Renal Division, Department of Medicine, Emory University School of Medicine, Renal Division 1639 Pierce Drive, NE, WMB Room 3313B, Atlanta, GA, 30322, USA. janet.klein@emory.edu
Kozlowski
S
S
Antoun
T Abi
TA
Sands
J M
JM
D000222:Adaptation, Physiological; D000315:Adrenalectomy; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000601:surgery*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008901:Mineralocorticoids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D015854:Up-Regulation; D000096982:Urea Transporters
D051399:Aquaporin 2; D026901:Membrane Transport Proteins; D008901:Mineralocorticoids; D013311:Streptozocin; D000096982:Urea Transporters; C496025:Aqp2 protein, rat