Journal of the American Society of Nephrology
2008 JASN IMPACT FACTOR 7.505 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


Published ahead of print on February 6, 2008
Journal of the American Society of Nephrology
© 2008 American Society of Nephrology
doi: 10.1681/ASN.2007060721
This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
ASN.2007060721v1
19/4/722    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Faulhaber-Walter, R.
Right arrow Articles by Schnermann, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Faulhaber-Walter, R.
Right arrow Articles by Schnermann, J.

Received June 29, 2007
Accepted on November 15, 2007

BASIC RESEARCH

Lack of A1 Adenosine Receptors Augments Diabetic Hyperfiltration and Glomerular Injury

Robert Faulhaber-Walter *, Limeng Chen *, Mona Oppermann *, Soo Mi Kim *, Yuning Huang *, Noriyuki Hiramatsu *, Diane Mizel *, Hiroshi Kajiyama *, Patricia Zerfas {dagger}, Josephine P. Briggs {ddagger}, Jeffrey B. Kopp *, and Jurgen Schnermann *1

*National Institute of Diabetes and Digestive and Kidney Diseases and {dagger}Veterinary Resources Program, Office of the Director, National Institutes of Health, Bethesda, and {ddagger}Howard Hughes Medical Institute, Chevy Chase, Maryland


1 To whom correspondence should be addressed. E-mail: jurgens{at}intra.niddk.nih.gov.


   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.




This article has been cited by other articles:


Home page
Am. J. Physiol. Renal Physiol.Home page
L. Nordquist, R. Brown, A. Fasching, P. Persson, and F. Palm
Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via efferent arteriole dilation and inhibition of tubular sodium reabsorption
Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1265 - F1272.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. Lau, I. Sudbury, M. Thomson, P. L. Howard, A. B. Magil, and W. A. Cupples
Salt-resistant blood pressure and salt-sensitive renal autoregulation in chronic streptozotocin diabetes
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2009; 296(6): R1761 - R1770.
[Abstract] [Full Text] [PDF]


Home page
CJASNHome page
E. Ritz
How Little Aldosterone is Able to Raise Blood Pressure?
Clin. J. Am. Soc. Nephrol., April 1, 2009; 4(4): 703 - 710.
[Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
S. M. Kim, F. Theilig, Y. Qin, T. Cai, D. Mizel, R. Faulhaber-Walter, H. Hirai, S. Bachmann, J. P. Briggs, A. L. Notkins, et al.
Dense-core vesicle proteins IA-2 and IA-2{beta} affect renin synthesis and secretion through the {beta}-adrenergic pathway
Am J Physiol Renal Physiol, February 1, 2009; 296(2): F382 - F389.
[Abstract] [Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
J. Peti-Peterdi, J. J. Kang, and I. Toma
Activation of the renal renin-angiotensin system in diabetes--new concepts
Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3047 - 3049.
[Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
S. M. Kim, C. Eisner, R. Faulhaber-Walter, D. Mizel, S. M. Wall, J. P. Briggs, and J. Schnermann
Salt sensitivity of blood pressure in NKCC1-deficient mice
Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1230 - F1238.
[Abstract] [Full Text] [PDF]


Home page
HypertensionHome page
M. W. Brands and H. Labazi
Role of Glomerular Filtration Rate in Controlling Blood Pressure Early in Diabetes
Hypertension, August 1, 2008; 52(2): 188 - 194.
[Full Text] [PDF]




HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP