Document Details
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Document Type |
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Article In Journal |
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Document Title |
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Modulation of single-nephron GFR in the db/db mouse model of type 2 diabetes mellitus. Modulation of single-nephron GFR in the db/db mouse model of type 2 diabetes mellitus. |
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Document Language |
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English |
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Abstract |
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The Kidney Research Centre, University of Ottawa, Ottawa, ON, Canada, K1H 8M5.
Hyperfiltration has been implicated in the progression toward diabetic nephropathy in type 2 diabetes mellitus (DM2). This study focuses for the first time on the in vivo modulation of single-nephron GFR (SNGFR) in the classic B6.Cg-m(+/+)Lepr(db)/J (db/db) mouse model of DM2. To obtain stable preparations, it was necessary to use a sustaining infusion of 3.3 ml.100 g body wt(-1) x h(-1), or higher. SNGFR (measured both proximally and distally) was greater in db/db vs. heterozygote (db/m) mice (P < 0.05) but not vs. the wild-type (WT) mice. The tubuloglomerular feedback (TGF) responses, determined as free-flow proximal vs. distal SNGFR differences, were significant in db/db mice (11.6 +/- 0.8 vs. 9.3 +/- 1.0 nl/min, P < 0.01), in db/m mice (8.0 +/- 0.8 vs. 7.2 +/- 0.6 nl/min, P < 0.02), and WT mice (9.9 +/- 0.6 vs. 8.9 +/- 0.7 nl/min, P < 0.05). After increasing the sustaining infusion in the db/db mice, to offset glycosuric urine losses, the SNGFR increased significantly, and the TGF response was abolished. In these volume-replete db/db mice, absolute fluid reabsorption measured both at the late proximal and distal tubular sites were significantly increased vs. db/m mice infused at 3.3 ml.100 g body wt(-1) x h(-1). After infusion of the neuronal nitric oxide synthase (nNOS) inhibitor S-methylthiocitrulline, SNGFR fell in both db/db and db/m mice. These studies show that SNGFR is elevated in this mouse model of DM2, is suppressed by nNOS inhibition, and is modulated by TGF influences that are altered by the diabetic state and responsive to changes in extracellular fluid volume. |
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ISSN |
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12897903 |
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Journal Name |
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Am J Physiol Regul Integr Comp Physiol |
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Volume |
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290 |
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Issue Number |
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4 |
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Publishing Year |
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1426 AH
2006 AD |
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Article Type |
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Article |
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Added Date |
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Sunday, May 30, 2010 |
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Researchers
| غدير مختار | Mokhtar, Ghadir | Researcher | Doctorate | |
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