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Downregulation of the (pro)renin receptor by insulin is potentiated by high glucose in mouse renal collecting duct cells
Author(s) -
Gonzalez Alexis A,
Rajo Marco,
Kassan Modar,
Matrougui Khalid,
Prieto Minolfa C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1068.11
Subject(s) - downregulation and upregulation , medicine , endocrinology , insulin , receptor , kidney , diabetic nephropathy , insulin receptor , diabetes mellitus , chemistry , renin–angiotensin system , insulin resistance , biochemistry , blood pressure , gene
Upregulation of the prorenin receptor (PRR) in glomeruli leads to diabetic nephropathy and high glucose increases PRR expression in mesangial cells in vitro. Angiotensin II (Ang II) upregulates PRR in the collecting duct (CD), which is the main source of prorenin in diabetes. However, there is no evidence indicating that the expression of the PRR in the CD is altered during this condition. To test the hypothesis that PRR expression in the CD is augmented by high glucose and that this effect is prevented by insulin, we examined the PRR mRNA levels in renal inner medullay tissues of db ‐/‐ knockout mice and wild type mice. PRR transcript levels were increased in db ‐/‐ knockout mice (129 ± 8 vs. 100 ± 6 %; P<0.05), which exhibited high blood glucose levels (431 ± 3 vs. 110 ± 11 mMol/L). Treatment with insulin (0.1U/implant × 30 days) prevented this upregulation yet in the presence of chronic Ang II infusion (68 ± 6 % vs. 100 ± 6 %; P<0.05). In M‐1 cells, a mouse collecting duct cell line grown in normal glucose levels (5 mM), PRR mRNA levels were downregulated by 100 nM insulin for 8 hours (68 ± 4 % vs. 100 ± 5 % P<0.05), and even further with concurrent treatment of 30 mM glucose (45 ± 8 % vs. 100 ± 5 %; P<0.001). No significant effects were found by high glucose alone. The downregulation of PRR expression in the CD by insulin even in the presence of high glucose suggest that insulin may protect the kidney from tubulointerstitial damage in diabetic subjects.