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- W2472380564 abstract "We generated insulin receptor (IR) knockout mice targeted specifically to the collecting duct principal cells (CD-KO) using standard Cre-lox mediated recombination. Mice with loxP sites flanking the IR gene were crossed with mice possessing Cre-recombinase driven by the AQP2-promoter. IR mRNA was found to be markedly decreased (5% of the WT) in the inner medulla homogenates of the CD-KO kidneys by real-time RT-PCR. Baseline values for blood pressure, assessed by radiotelemetry, were not different (mm Hg): 103 ± 6 (WT) versus 111 ± 2 (CD-KO); however the ratio of night- to day-time blood pressure was decreased in CD-KO (1.08) versus WT (1.13), suggesting that CD-KO may have impaired diurnal cycling of blood pressure. Previously, we demonstrated that mice with knockout of the IR from thick ascending limb through the CD (TAL-CD-KO mice) had impaired/delayed natriuretic responses to oral or intraperitoneal (ip) NaCl or water loads. The CD-KO mice, likewise had a significantly blunted Na+excretion in response to ip water (0.2 ml) as compared to WT littermates: 22.1 ± 2.7 (CD-KO) versus 45.8 ± 8.7(WT) μmols Na+ excreted in 4 hours, p = 0.040. Mice were also placed on high-NaCl diet to test salt-sensitivity of Na+ transporter regulation. After 4 weeks, mice were euthanized and western blotting was performed on whole kidney homogenates. The post-macula densa sodium transporters/channel subunits α- and β-ENaC (epithelial sodium channel subunits), and NCC (thiazide-sensitive Na-Cl cotransporter) band densities were increased an average of 15.7%, 14.8%, and 28.3 %, respectively in CD-KO relative to WT. However, CD-KO had reduced total abundance of the γ-subunit of ENaC (20%). These results suggest a physiologic role for the insulin receptor in CD principal cells to modulate both blood pressure and sodium balance. Support-NIH" @default.
- W2472380564 created "2016-07-22" @default.
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- W2472380564 date "2008-03-01" @default.
- W2472380564 modified "2023-09-26" @default.
- W2472380564 title "Blood pressure and sodium transporter and channel regulation in mice with targeted knockout of the insulin receptor from collecting duct principal cells" @default.
- W2472380564 doi "https://doi.org/10.1096/fasebj.22.1_supplement.1158.25" @default.
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