| First Author | Faulhaber-Walter R | Year | 2008 |
| Journal | J Am Soc Nephrol | Volume | 19 |
| Issue | 4 | Pages | 722-30 |
| PubMed ID | 18256360 | Mgi Jnum | J:149926 |
| Mgi Id | MGI:3849378 | Doi | 10.1681/ASN.2007060721 |
| Citation | Faulhaber-Walter R, et al. (2008) Lack of A1 adenosine receptors augments diabetic hyperfiltration and glomerular injury. J Am Soc Nephrol 19(4):722-30 |
| abstractText | 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. |
