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


METHODS
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.


RESULTS
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.


CONCLUSIONS
A(1)Rs determine glomerular hyperfiltration and the salt paradox in early diabetes, which is consistent with the tubulocentric principle.
Vallon
Volker
V
Department of Medicine, University of California San Diego, San Diego, Calif., USA. vvallon@ucsd.edu
Schroth
Jana
J
Satriano
Joseph
J
Blantz
Roland C
RC
Thomson
Scott C
SC
Rieg
Timo
T
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D004039:Diet, Sodium-Restricted; D004326:Drinking; D004435:Eating; D025461:Feedback, Physiological; D005919:Glomerular Filtration Rate; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043682:Receptor, Adenosine A1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000378:metabolism*; D013997:Time Factors
D001786:Blood Glucose; D043682:Receptor, Adenosine A1; D017673:Sodium Chloride, Dietary; D000450:Aldosterone