Sphingomyelinase stimulates 2-deoxyglucose uptake by skeletal muscle.
Sphingomyelinase stimulates 2-deoxyglucose uptake by skeletal muscle.
复制标题
鞘磷脂酶刺激骨骼肌摄取 2-脱氧葡萄糖。
DOI：
10.1042/bj3130215
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Smith,TR
中科院分区：
文献类型：
--
作者：
Turinsky,J;Nagel,GW;Elmendorf,JS;Damrau-Abney,A;Smith,TR
研究了鞘磷脂酶、磷酸胆碱、N-乙酰鞘氨醇（C2-神经酰胺）、N-己酰鞘氨醇（C6-神经酰胺）和鞘氨醇对大鼠比目鱼肌细胞基础和胰岛素刺激的2-脱氧-D-葡萄糖积累的影响。用鞘磷脂酶（100或200 m单位/ml）预孵育肌肉1或2小时，与相同胰岛素浓度下研究的对照肌肉相比，基础2-脱氧葡萄糖摄取增加29- 91%，0.1和1.0 m单位/ml胰岛素分别增加32-82%和19-25%。70 μM细胞松弛素B可抑制鞘磷脂酶诱导的基础和胰岛素刺激的2-脱氧葡萄糖摄取增加91%，表明其涉及葡萄糖转运蛋白。鞘磷脂酶对细胞内不经葡萄糖转运蛋白转运的L-葡萄糖的积累无影响。用50 μM磷酸胆碱、50 μM C2-神经酰胺或50 μM C6-神经酰胺预孵育肌肉不能再现鞘磷脂酶诱导的2-脱氧葡萄糖摄取增加。用50 μM鞘氨醇预孵育肌肉使基础2-脱氧葡萄糖转运增加32%，但使对0.1和1.0 M单位/ml胰岛素的反应分别降低17%和27%。鞘磷脂酶对基础和胰岛素诱导的2-脱氧葡萄糖摄取的刺激作用不受从孵育培养基中去除Ca 2+或丹曲林（肌浆网Ca 2+释放的抑制剂）的影响。这表明Ca 2+不介导鞘磷脂酶对2-脱氧葡萄糖摄取的作用。鞘磷脂酶对胰岛素受体酪氨酸激酶和磷脂酰肌醇3-激酶的基础活性和胰岛素刺激活性也没有影响。此外，1和5 μM磷脂酰肌醇3-激酶抑制剂渥曼青霉素不能抑制鞘磷脂酶诱导的2-脱氧葡萄糖摄取增加。这些结果表明，鞘磷脂酶不增加2-脱氧葡萄糖摄取刺激胰岛素受体或胰岛素转导途径的初始步骤。这些数据表明，鞘磷脂酶增加骨骼肌的基础和胰岛素刺激的2-脱氧葡萄糖摄取的可能性，作为一个未知的受体后效应的结果。
The effects of sphingomyelinase, phosphorylcholine,N-acetylsphingosine (C2-ceramide),N-hexanoylsphingosine (C6-ceramide) and sphingosine on basal and insulin-stimulated cellular accumulation of 2-deoxy-D-glucose in rat soleus muscles were investigated. Preincubation of muscles with sphingomyelinase (100 or 200 m-units/ml) for 1 or 2 h augmented basal 2-deoxyglucose uptake by 29-91%, and that at 0.1 and 1.0 m-unit of insulin/ml by 32-82% and 19-25% respectively compared with control muscles studied at the same insulin concentrations. The sphingomyelinase-induced increase in basal and insulin-stimulated 2-deoxyglucose uptake was inhibited by 91% by 70 μM cytochalasin B, suggesting that it involves glucose transporters. Sphingomyelinase had no effect on the cellular accumulation ofL-glucose, which is not transported by glucose transporters. The sphingomyelinase-induced increase in 2-deoxyglucose uptake could not be reproduced by preincubating the muscles with 50 μM phosphorylcholine, 50 μM C2-ceramide or 50 μM C6-ceramide. Preincubation of muscles with 50 μM sphingosine augmented basal 2-deoxyglucose transport by 32%, but reduced the response to 0.1 and 1.0 m-unit of insulin/ml by 17 and 27% respectively. The stimulatory effect of sphingomyelinase on basal and insulin-induced 2-deoxyglucose uptake was not influenced by either removal of Ca2+from the incubation medium or dantrolene, an inhibitor of Ca2+release from the sarcoplasmic reticulum. This demonstrates that Ca2+does not mediate the action of sphingomyelinase on 2-deoxyglucose uptake. Sphingomyelinase also had no effect on basal and insulin-stimulated activities of insulin receptor tyrosine kinase and phosphatidylinositol 3-kinase. In addition, 1 and 5 μM wortmannin, an inhibitor of phosphatidylinositol 3-kinase, failed to inhibit the sphingomyelinase-induced increase in 2-deoxyglucose uptake. These results suggest that sphingomyelinase does not increase 2-deoxyglucose uptake by stimulating the insulin receptor or the initial steps of the insulin-transduction pathway. The data suggest the possibility that sphingomyelinase increases basal and insulin-stimulated 2-deoxyglucose uptake in skeletal muscle as the result of an unknown post-receptor effect.