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Nephron Physiol. 2009;111(3):p30-8. doi: 10.1159/000208211. Epub 2009 Mar 10.

Adenosine A(1) receptors determine glomerular hyperfiltration and the salt paradox in early streptozotocin diabetes mellitus.

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Department of Medicine, University of California San Diego, San Diego, Calif., USA.



In early type 1 diabetes mellitus, changes in proximal reabsorption influence glomerular filtration rate (GFR) through tubuloglomerular feedback (TGF). Due to TGF, a primary increase in proximal reabsorption causes early diabetic hyperfiltration, while a heightened sensitivity of the proximal tubule to dietary salt leads to the so-called salt paradox, where a change in dietary salt causes a reciprocal change in GFR ('tubulocentric principle'). Here, experiments were performed in adenosine A(1) receptor knockout mice (A(1)R-/-), which lack an immediate TGF response, to determine whether A(1)Rs are essential for early diabetic hyperfiltration and the salt paradox.


GFR was measured by inulin disappearance in conscious A(1)R-/- and wild-type (WT) mice after 4 weeks of streptozotocin diabetes on a control NaCl diet (1%), and measurements were repeated after 6 days of equilibration on a low-NaCl (0.1%) or a high-NaCl (4%) diet.


A(1)R-/- and WT were similar with respect to blood glucose, dietary intakes and body weight changes on a given diet. Diabetic hyperfiltration occurred in WT, but was blunted in A(1)R-/-. A reciprocal relationship between GFR and dietary salt was found in WT diabetics, but not A(1)R-/- diabetics or nondiabetics of either strain.


A(1)Rs determine glomerular hyperfiltration and the salt paradox in early diabetes, which is consistent with the tubulocentric principle.

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