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Potential Role of the Epithelial Na+ Channel α Subunit Cleavage in the Regulation of Urinary Na+ Excretion During Insulin Resistance
Author(s) -
Balayan Shaina S.,
Rodriguez Ruben,
Viscarra Jose,
Nishiyama Akira,
Awayda Mouhamed S.,
Ortiz Rudy M.
Publication year - 2011
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.25.1_supplement.1041.10
Subject(s) - protein subunit , insulin resistance , epithelial sodium channel , urinary system , excretion , cleavage (geology) , chemistry , endocrinology , medicine , insulin , microbiology and biotechnology , biology , biochemistry , sodium , gene , paleontology , fracture (geology) , organic chemistry
Epithelial Na + Channel (ENaC) regulates Na + transport and balance, and is regulated by the insulin signaling pathway in cultured cells; however, the in vivo regulation by insulin is not well described. Moreover, the interaction between insulin and aldosterone signaling on ENaC in vivo is also undetermined. To study this, we examined the effects of an angiotensin receptor blocker (ARB) on plasma aldosterone and ENaC in five groups of rats: 1) LETO (control strain), 2) untreated OLETF, 3) OLETF + 5% glucose water (OLETF HG), 4) OLETF + ARB (10 mg olmesartan/kg/d) and 5) OLETF HG + ARB (OLETF HG/ARB). ARB reduced SBP in both OLETF (104 ± 5 vs 141 ± 2 mmHg) and HG (105 ± 5 vs 150 ± 2 mmHg). ARB decreased insulin 58% and aldosterone 71% in unsupplemented conditions. HG exacerbated plasma insulin but decreased aldosterone 2‐fold. ARB (35.3 ± 3.9 uU/ml) was effective in normalizing the increase in plasma insulin associated with HG (82.4 ± 9.5 μU/ml). The cleaved subunit of α ENaC (65 kDa) positively correlated with a decrease in plasma aldosterone suggesting that α‐cleavage and presumably channel activation is associated with aldosterone in insulin resistant conditions. Increased α ENaC corresponded to a decrease in urinary Na + excretion (mmol/d) and vice versa, indicating that cleavage in vivo is likely a key component in the regulation of Na + excretion and ultimately blood pressure during insulin resistance. NIH NCMHD 9T37MD001480.