A muscle-specific isoform of neuronal nitric oxide synthase is phosphorylated in response to insulin
Presentation Number: MON-852
Date of Presentation: June 17th, 2013
Kathryn Hinchee-Rodriguez*1, Neha Garg2, Priya Venkatakrishnan3, Madeline G Roman4, Martin L Adamo4, Bettie Sue Masters1 and Linda J Roman1
1Univ of Texas Hlth Sci Ctr, San Antonio, TX, 2Harvard Medical School, Boston, MA, 3Integrity Bio, Newbury Park, CA, 4UTHSCSA, San Antonio, TX
Nitric oxide (NO), a signaling molecule produced 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 are decreased. Additionally, NO production increases in normal adults with insulin, but not in T2DM adults. The primary NOS isoform in skeletal muscle is neuronal NOSμ (nNOSμ), which differs from the more ubiquitous 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 plateaued through 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 wild-type C57Bl/6 mice.
Nothing to Disclose: KH, NG, PV, MGR, MLA, BSM, LJR