In:
Nephron Physiology, S. Karger AG, Vol. 111, No. 3 ( 2009-3-10), p. p30-p38
Abstract:
〈 i 〉 Background: 〈 /i 〉 In early type 1 diabetes mellitus, changes in proximal reabsorption influence glomerular filtration rate (GFR) through tubuloglomerular feedback (TGF). Due to TGF, a 〈 i 〉 primary 〈 /i 〉 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 〈 sub 〉 1 〈 /sub 〉 receptor knockout mice (A 〈 sub 〉 1 〈 /sub 〉 R–/–), which lack an immediate TGF response, to determine whether A 〈 sub 〉 1 〈 /sub 〉 Rs are essential for early diabetic hyperfiltration and the salt paradox. 〈 i 〉 Methods: 〈 /i 〉 GFR was measured by inulin disappearance in conscious A 〈 sub 〉 1 〈 /sub 〉 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. 〈 i 〉 Results: 〈 /i 〉 A 〈 sub 〉 1 〈 /sub 〉 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 〈 sub 〉 1 〈 /sub 〉 R–/–. A reciprocal relationship between GFR and dietary salt was found in WT diabetics, but not A 〈 sub 〉 1 〈 /sub 〉 R–/– diabetics or nondiabetics of either strain. 〈 i 〉 Conclusion: 〈 /i 〉 A 〈 sub 〉 1 〈 /sub 〉 Rs determine glomerular hyperfiltration and the salt paradox in early diabetes, which is consistent with the tubulocentric principle.
Type of Medium:
Online Resource
ISSN:
1660-2137
Language:
English
Publisher:
S. Karger AG
Publication Date:
2009
detail.hit.zdb_id:
2098340-2
