Modulation of single-nephron GFR in the db/db mouse model of type 2 diabetes mellitus. II. Effects of renal mass reduction

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
David Z LevineSusan J Robertson

Abstract

This study examines for the first time the effects of uninephrectomy (Nx) on modulation of whole kidney glomerular filtration rate (GFR), single-nephron GFR (SNGFR), and progression of diabetic nephropathy in the db/db mouse model of type 2 diabetes mellitus. To characterize SNGFR and tubuloglomerular feedback (TGF) responses to Nx and chronic neuronal nitric oxide synthase inhibition in the db/db mouse, we studied the effects of Nx on whole kidney GFR, SNGFR, and TGF characteristics in db/db and wild-type (WT) mice after Nx or sham Nx. We also documented progression of glomerular changes over a 6-mo period. Whole kidney GFR and SNGFR were significantly higher in db/db Nx than db/db sham mice, without change in proximal tubule reabsorptive rates. The TGF responses, determined as proximal-distal SNGFR differences, were brisk: 12.1 +/- 1.0 vs. 8.4 +/- 0.6 nl/min in WT sham (P < 0.05), 15.7 +/- 1.0 vs. 12.0 +/- 1.0 nl/min in WT Nx (P < 0.05), and 17.8 +/- 1.3 vs. 14.3 +/- 1.0 nl/min in db/db Nx (P < 0.05) mice. Chronic ingestion of the neuronal nitric oxide synthase inhibitor S-methylthiocitrulline for 2-3 wk after Nx had no effect on SNGFR or the TGF response. These studies show further elevations in whole kidney GFR and SNGFR in...Continue Reading

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Citations

May 5, 2006·Current Hypertension Reports·David Z Levine
Aug 3, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·David Z I CherneyEtienne B Sochett
Dec 21, 2010·Mathematical Biosciences·Natasha K MartinPhilip K Maini
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Apr 3, 2015·Physiological Reviews·Mattias CarlströmWilliam J Arendshorst
Dec 18, 2013·Transplantation·Sindhu ChandranDavid M Wojciechowski
Dec 15, 2010·American Journal of Physiology. Renal Physiology·G H Tesch, A K H Lim
Dec 20, 2018·NPJ Systems Biology and Applications·Hari Shankar MahatoK Melissa Hallow
Mar 15, 2019·Journal of the American Society of Nephrology : JASN·Jie ZhangRuisheng Liu
Feb 18, 2021·Journal of Laparoendoscopic & Advanced Surgical Techniques. Part a·Mustafa ErkocHasan A Atalay
Sep 9, 2021·Disease Models & Mechanisms·Frederikke E SembachMette V Østergaard

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