NITRIC-OXIDE STIMULATES GLUCOSE-TRANSPORT AND METABOLISM IN RAT SKELETAL-MUSCLE IN-VITRO

1. The effects of the nitric oxide (NO) donor sodium nitroprusside (SN P) on the rates of glucose transport and utilization and its interacti on with insulin were investigated in rat soleus muscle in vitro. SNP s timulated the rate of 2-deoxyglucose transport and insulin-mediated (1 00 mu-units/ml) rates of both net and [C-14]lactate release and the ra te of glucose oxidation. The effects of SNP were independent of the co ncentration-dependent effects of insulin on glucose metabolism. 2. SNP stimulated the insulin-stimulated rates of net and [C-14]lactate rele ase and glucose oxidation in a concentration-dependent manner. The rat e of [C-14]lactate release was also stimulated by another NO donor, op ylammonio)butyl]-amino)-diazen-1-ium-1,2-diolate (spermine NONOate). 3 . SNP at 5, 10 and 15 mM inhibited the insulin-stimulated rate of glyc ogen synthesis and this rate was further decreased at 20 and 25 mM SNP . SNP did not affect the rate of glycogen synthesis in the absence of insulin. 4. Haemoglobin, which is a NO scavenger, prevented the stimul ation of the rates of [C-14]lactate release by SNP or spermine NONOate . 5. The cGMP content was increased maximally (by approx. 80-fold) wit hin 15 min by SNP (15 mM). The cGMP content, raised maximally by SNP, was significantly decreased by the guanylate cyclase inhibitor LY-8358 3 (10 mu M). The cGMP analogue 8-bromo-cGMP (100 mu M) significantly i ncreased the rate of net lactate release. 6. LY-83583 significantly in hibited SNP-stimulated rates of 2-deoxyglucose transport, [C-14]lactat e release and glucose oxidation. Methylene Blue (another guanylate cyc lase inhibitor) also inhibited SNP-stimulated rates of [C-14]lactate r elease. 7. The results suggest that in rat skeletal muscle: (a) nitric oxide (from SNP or spermine NONOate) increases the rate of glucose tr ansport and metabolism, an effect independent of insulin; (b) SNP inhi bits insulin-mediated rates of glycogen synthesis; (c) SNP stimulates cGMP formation, which mediates, at least partly, the effects on glucos e metabolism; (d) nitric oxide-mediated stimulation of glucose utiliza tion might occur in fibre contraction. The implications of the effects of NO on glucose metabolism are discussed.