5`-aminoimidazole-4-carboxyamide-ribonucleoside- activated glucose transport is not prevented by nitric oxide synthase inhibition in rat isolated skeletal muscle

1. The nucleoside intermediate 5\u27-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) activates skeletal muscle AMP-activated protein kinase (AMPK) and increases glucose uptake. The AMPK phosphorylates neuronal nitric oxide synthase (nNOS)&micro; in skeletal muscle fibres. There is evidence that both AMPK and nNOS&micro; may be involved in the regulation of contraction-stimulated glucose uptake.2. We examined whether both AICAR- and contraction-stimulated glucose uptake were mediated by NOS in rat skeletal muscle.3. Rat isolated epitrochlearis muscles were subjected in vitro to electrically stimulated contractions for 10 min and/or incubated in the presence or absence of AICAR (2 mmol/L) or the NOS inhibitor NG-monomethyl-l-arginine (l-NMMA; 100 &micro;mol/L).4. Muscle contraction significantly (P &lt; 0.05) altered the metabolic profile of the muscle. In contrast, AICAR and l-NMMA had no effect on the metabolic profile of the muscle, except that AICAR increased muscle 5\u27-aminoimidazole-4-carboxyamide-ribonucleotide (ZMP) and AICAR content. Nitric oxide synthase inhibition caused a small but significant (P &lt; 0.05) reduction in basal 3-O-methylglucose transport, which was observed in all treatments. 5\u27-Aminoimidazole-4-carboxyamide-ribonucleoside significantly increased (P &lt; 0.05) glucose transport above basal, with NOS inhibition decreasing this slightly (increased by 209% above basal compared with 184% above basal with NOS inhibition). Contraction significantly increased glucose transport above basal, with NOS inhibition substantially reducing this (107% increase vs 31% increase). 5\u27-Aminoimidazole-4-carboxyamide-ribonucleoside plus contraction in combination were not additive on glucose transport.5. These results suggest that NO plays a role in basal glucose uptake and may regulate contraction-stimulated glucose uptake. However, NOS/nitric oxide do not appear to be signalling intermediates in AICAR-stimulated skeletal muscle glucose uptake.<br /