| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
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Received June 29, 2007
Accepted on November 15, 2007
BASIC RESEARCH |
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,
*National Institute of Diabetes and Digestive and Kidney Diseases and
Veterinary Resources Program, Office of the Director, National Institutes of Health, Bethesda, and
Howard Hughes Medical Institute, Chevy Chase, Maryland
1 To whom correspondence should be addressed. E-mail: jurgens{at}intra.niddk.nih.gov.
| Abstract |
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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.
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