Lack of A1 Adenosine Receptors Augments Diabetic Hyperfiltration and Glomerular Injury
Open Access
- 1 April 2008
- journal article
- Published by Wolters Kluwer Health in Journal of the American Society of Nephrology
- Vol. 19 (4) , 722-730
- https://doi.org/10.1681/asn.2007060721
Abstract
Intraglomerular hypertension and glomerular hyperfiltration likely contribute to the pathogenesis of diabetic nephropathy, and tubuloglomerular feedback (TGF) has been suggested to play a role in diabetic hyperfiltration. A1 adenosine receptor (A1AR) null mice lack a TGF response, so this model was used to investigate the contribution of TGF to hyperfiltration in diabetic Ins2+/− Akita mice. TGF responses in Ins2+/− A1AR−/− double mutants were abolished, whereas they were attenuated in Ins2+/− mice. GFR, assessed at 14, 24, and 33 wk, was approximately 30% higher in Ins2+/− than in wild-type (WT) mice and increased further in Ins2+/− A1AR−/− mutants (P < 0.01 versus both WT and Ins2+/− mice at all ages). Histologic evidence of glomerular injury and urinary albumin excretion were more pronounced in double-mutant than single-mutant or WT mice. In summary, the marked elevation of GFR in diabetic mice that lack a TGF response indicates that TGF is not required to cause hyperfiltration in the Akita model of diabetes. Rather, an A1AR-dependent mechanism, possibly TGF, limits the degree of diabetic hyperfiltration and nephropathy.Keywords
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