Neuronal nitric oxide synthase is phosphorylated in response to insulin stimulation in skeletal muscle

Kathryn Hinchee-Rodriguez, Neha Garg, Priya Venkatakrishnan, Madeline G. Roman, Martin L. Adamo, Bettie Sue Masters, Linda J. Roman

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Type 2 Diabetes (T2DM) is the seventh leading cause of death in the United States, and is quickly becoming a global pandemic. T2DM results from reduced insulin sensitivity coupled with a relative failure of insulin secretion. Reduced insulin sensitivity has been associated with reduced nitric oxide synthase (NOS) activity and impaired glucose uptake in T2DM skeletal muscle. Upon insulin stimulation, NO synthesis increases in normal adult skeletal muscle, whereas no such increase is observed in T2DM adults. Endothelial NOS is activated by phosphorylation in the C-terminal tail in response to insulin. Neuronal NOS (nNOS), the primary NOS isoform in skeletal muscle, contains a homologous phosphorylation site, raising the possibility that nNOS, too, may undergo an activating phosphorylation event upon insulin treatment. Yet it remains unknown if or how nNOS is regulated by insulin in skeletal muscle. Data shown herein indicate that nNOS is phosphorylated in response to insulin in skeletal muscle and that this phosphorylation event occurs rapidly in C2C12 myotubes, resulting in increased NO production. In vivo phosphorylation of nNOS was also observed in response to insulin in mouse skeletal muscle. These results indicate, for the first time, that nNOS is phosphorylated in skeletal muscle in response to insulin and in association with increased NO production.

Original languageEnglish (US)
Pages (from-to)501-505
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Jun 7 2013


  • Insulin signaling
  • Myotubes
  • Nitric oxide synthase
  • Skeletal muscle
  • Type 2 Diabetes (T2DM)

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Neuronal nitric oxide synthase is phosphorylated in response to insulin stimulation in skeletal muscle'. Together they form a unique fingerprint.

Cite this