Lack of A1 adenosine receptors augments diabetic hyperfiltration and glomerular injury

被引：87

作者：

Faulhaber-Walter, Robert ^{[1
]}

Chen, Limeng ^{[1
]}

Oppermann, Mona ^{[1
]}

Kim, Soo Mi ^{[1
]}

Huang, Yuning ^{[1
]}

Hiramatsu, Noriyuki ^{[1
]}

Mizel, Diane ^{[1
]}

Kajiyama, Hiroshi ^{[1
]}

Zerfas, Patricia ^{[2
]}

Briggs, Josephine P. ^{[3
]}

Kopp, Jeffrey B. ^{[1
]}

Schnermann, Jurgen ^{[1
]}

机构：

[1] NIDDK, NIH, Bethesda, MD 20892 USA

[2] NIDDK, Vet Resources Program, Bethesda, MD USA

[3] Howard Hughes Med Inst, Chevy Chase, MD USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2008年 / 19卷 / 04期

关键词：

D O I：

10.1681/ASN.2007060721

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 TGIF 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.

引用

页码：722 / 730

页数：9

共 38 条

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