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

Abstract

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.

CONCLUSION:

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

• Authors: Volker Vallon, Jana Schroth, Joseph Satriano, Roland C Blantz, Scott C Thomson, Timo Rieg
• Journal: Nephron. Physiology (Nephron Physiol) Vol. 111 Issue 3 Pg. p30-8 ( 2009) ISSN: 1660-2137 [Electronic] Switzerland
• PMID: 19276628 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Blood Glucose
• Receptor, Adenosine A1
• Sodium Chloride, Dietary
• Aldosterone

Topics

• Aldosterone (blood)
• Animals
• Blood Glucose (metabolism)
• Body Weight
• Diabetes Mellitus, Experimental (metabolism, physiopathology)
• Diabetic Nephropathies (metabolism, physiopathology)
• Diet, Sodium-Restricted
• Drinking
• Eating
• Feedback, Physiological
• Glomerular Filtration Rate
• Kidney Tubules, Proximal (metabolism, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptor, Adenosine A1 (deficiency, genetics, metabolism)
• Sodium Chloride, Dietary (metabolism)
• Time Factors