Abstract
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 language | English (US) |
|---|---|
| Pages (from-to) | 501-505 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 435 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jun 7 2013 |
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Keywords
- Insulin signaling
- Myotubes
- Nitric oxide synthase
- Skeletal muscle
- Type 2 Diabetes (T2DM)
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Molecular Biology
Cite this
Neuronal nitric oxide synthase is phosphorylated in response to insulin stimulation in skeletal muscle. / Hinchee-Rodriguez, Kathryn; Garg, Neha; Venkatakrishnan, Priya; Roman, Madeline G.; Adamo, Martin L; Masters, Bettie Sue; Roman, Linda J.
In: Biochemical and Biophysical Research Communications, Vol. 435, No. 3, 07.06.2013, p. 501-505.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neuronal nitric oxide synthase is phosphorylated in response to insulin stimulation in skeletal muscle
AU - Hinchee-Rodriguez, Kathryn
AU - Garg, Neha
AU - Venkatakrishnan, Priya
AU - Roman, Madeline G.
AU - Adamo, Martin L
AU - Masters, Bettie Sue
AU - Roman, Linda J.
PY - 2013/6/7
Y1 - 2013/6/7
N2 - 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.
AB - 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.
KW - Insulin signaling
KW - Myotubes
KW - Nitric oxide synthase
KW - Skeletal muscle
KW - Type 2 Diabetes (T2DM)
UR - http://www.scopus.com/inward/record.url?scp=84878982395&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878982395&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2013.05.020
DO - 10.1016/j.bbrc.2013.05.020
M3 - Article
C2 - 23680665
AN - SCOPUS:84878982395
VL - 435
SP - 501
EP - 505
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -