Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle.
BACKGROUND
Evidence demonstrates that exogenously administered nitric oxide (NO) can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the early events in insulin signaling in rat skeletal myocytes.


RESULTS
Skeletal muscle cells from 6-8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml) in the presence or absence of glucose (25 mM) and insulin (100 nM). Cellular insulin receptor-beta levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO).


CONCLUSIONS
These data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.
Badal
Simone
S
Department of Basic Medical Sciences, Section of Biochemistry, The University of the West Indies, Kingston, Jamaica. simone_badal@hotmail.com
Brown
Paul D
PD
Ragoobirsingh
Dalip
D
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects*
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D020030:Nitric Oxide Donors; D010750:Phosphoproteins; D009569:Nitric Oxide; D011972:Receptor, Insulin