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A muscle‐specific isoform of neuronal nitric oxide synthase is phosphorylated in response to insulin
Author(s) -
HincheeRodriguez Kathryn,
Garg Neha,
Venkatakrishnan Priya,
Roman Madeline G.,
Adamo Martin,
Masters Bettie Sue,
Roman Linda J.
Publication year - 2013
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.27.1_supplement.1051.2
Subject(s) - medicine , insulin , endocrinology , phosphorylation , skeletal muscle , nitric oxide , insulin resistance , insulin receptor , nitric oxide synthase , chemistry , glucose uptake , biology , biochemistry
Nitric oxide (NO), a signaling molecule made by nitric oxide synthases (NOSs), is implicated in skeletal muscle glucose uptake and insulin sensitivity. In skeletal muscle from adults with Type 2 Diabetes (T2DM), insulin‐stimulated NO production and glucose disposal is decreased. Additionally, NO production increases in normal adults with insulin, but not in T2DM adults. The primary NOS form in skeletal muscle is nNOSμ, which differs from nNOSα by a 34‐amino acid insert into a known regulatory region. While it is well‐documented that insulin causes endothelial NOS (eNOS) activation via serine phosphorylation in the C‐terminal tail, little is known of nNOSμ function or response to insulin. Because nNOS contains analogous serine residues in its C‐terminus, phosphorylation of nNOS in C2C12 myotubes was examined at 0–60 minutes after 100nM insulin exposure. Insulin treatment resulted in increased phosphorylation of the nNOS variants at early time points (up to 15 min), but decreased at later time points. Additionally, under conditions of free fatty acid (FFA)‐induced insulin resistance, a further increase in phospho‐nNOS levels was observed, suggesting that FFA may have a synergistic effect on nNOS phosphorylation with insulin stimulation. nNOS phosphorylation was also observed in vivo in muscle tissue from insulin‐treated WT C57/Bl6 mice. Supported by NIH GM052419 to LJR and BSM.