title: Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle.
abstract: 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.
authors.affiliation: Department of Basic Medical Sciences, Section of Biochemistry, The University of the West Indies, Kingston, Jamaica. simone_badal@hotmail.com
authors.forename: Simone
authors.initials: S
authors.lastname: Badal
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.forename: Dalip
authors.initials: D
authors.lastname: Ragoobirsingh
mesh_terms: 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*
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D020030:Nitric Oxide Donors; D010750:Phosphoproteins; D009569:Nitric Oxide; D011972:Receptor, Insulin