Jensen J, Sharikabad M N, Østbye K M, Melien Ø, Brørs O
Department of Physiology, National Institute of Occupational Health, Oslo, Norway.
Arch Physiol Biochem. 2003 Jul;111(3):239-45. doi: 10.1076/apab.111.3.239.23463.
Sodium nitroprusside (SNP), a nitric oxide (NO.) donor, stimulates glucose uptake in skeletal muscle. We investigated the stimulatory effect of SNP on glucose uptake in cardiomyocytes and the possible role of soluble guanylate cyclase, phosphatidylinositol-3-kinase (PI-3-kinase) and the mitogen-activated protein kinases (MAPKs). Cardiomyocytes were isolated from adult male Wistar rats by trypsin/collagenase perfusion and glucose uptake determined from the accumulation of 3H-2-deoxyglucose. SNP caused a dose-dependent increase in glucose uptake with 200-300% increase at 30 mM. Cytochalasin B completely prevented the SNP-induced increase in glucose uptake. 8-Br-cGMP (100 microM) and the NO. donor spermineNONOate (100 microM) were without effect on basal glucose uptake. SNP-stimulated glucose uptake was not inhibited by the guanylate cyclase inhibitor ODQ (10 microM). Sodium ferrocyanide (Na4Fe(CN)6), a compound structurally related to SNP, but without any NO. group, also stimulated glucose uptake in cardiomyocytes suggesting that the effect of SNP could be unrelated to liberation of NO. Wortmannin, an inhibitor of PI-3-kinase, inhibited insulin-stimulated glucose uptake completely but did not affect SNP-stimulated glucose uptake. SNP-stimulated glucose uptake was inhibited by 50 microM PD 098059 (inhibitor of the MAPK-kinases that activate external regulated kinase [ERK1/2]) and by 50 microM SB203580 (inhibitor of p38MAPK). In conclusion, high SNP concentrations dose-dependently stimulate glucose uptake in cardiomyocytes and our data suggest a role for MAPK signalling, but not PI-3-kinase and soluble guanylate cyclase, in stimulation of glucose uptake.
硝普钠（SNP）是一种一氧化氮（NO.）供体，可刺激骨骼肌摄取葡萄糖。我们研究了SNP对心肌细胞摄取葡萄糖的刺激作用以及可溶性鸟苷酸环化酶、磷脂酰肌醇-3-激酶（PI-3-激酶）和丝裂原活化蛋白激酶（MAPK）的可能作用。通过胰蛋白酶/胶原酶灌注从成年雄性Wistar大鼠中分离心肌细胞，并根据3H-2-脱氧葡萄糖的积累来测定葡萄糖摄取。SNP导致葡萄糖摄取呈剂量依赖性增加，在30 mM时增加200-300%。细胞松弛素B完全阻止了SNP诱导的葡萄糖摄取增加。8-溴-cGMP（100 microM）和NO.供体精胺NONOate（100 microM）对基础葡萄糖摄取没有影响。SNP刺激的葡萄糖摄取不受鸟苷酸环化酶抑制剂ODQ（10 microM）的抑制。亚铁氰化钠（Na4Fe(CN)6）是一种在结构上与SNP相关但没有任何NO.基团的化合物，它也刺激心肌细胞摄取葡萄糖，这表明SNP的作用可能与NO.释放无关。渥曼青霉素是一种PI-3-激酶抑制剂，它完全抑制胰岛素刺激的葡萄糖摄取，但不影响SNP刺激的葡萄糖摄取。SNP刺激的葡萄糖摄取受到50 microM PD 098059（激活细胞外调节激酶[ERK1/2]的MAPK激酶抑制剂）和50 microM SB203580（p38MAPK抑制剂）的抑制。总之，高浓度SNP剂量依赖性地刺激心肌细胞摄取葡萄糖，我们的数据表明MAPK信号通路在刺激葡萄糖摄取中起作用，但PI-3-激酶和可溶性鸟苷酸环化酶不起作用。
