EFFECTS OF PHENYLARSINE OXIDE ON STIMULATION OF GLUCOSE-TRANSPORT IN RAT SKELETAL-MUSCLE

EFFECTS OF PHENYLARSINE OXIDE ON STIMULATION OF GLUCOSE-TRANSPORT IN RAT SKELETAL-MUSCLE
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DOI:
10.1152/ajpcell.1990.258.4.c648
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发表时间:
1990-04-01
影响因子:
--
通讯作者:
HOLLOSZY, JO
HOLLOSZY, JO
中科院分区:
其他
文献类型:
--
作者:
HENRIKSEN, EJ;HOLLOSZY, JO

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三价砷苯larsine oxide (PAO)通过与邻近的巯基直接相互作用抑制胰岛素刺激的葡萄糖在脂肪细胞和骨骼肌中的转运。在肌肉中,葡萄糖运输也被收缩活动和缺氧激活。因此,本研究的目的是研究邻近的巯基是否参与刺激离体大鼠耳蜗外肌缺氧或收缩时的葡萄糖转运活性。(5 .)M)导致不可代谢的葡萄糖类似物3- o -甲基葡萄糖(3-MG)的运输速率增加两倍,这被细胞松弛素B、邻近的二硫醇二巯基丙醇、丹曲烯或9-氨基吡啶完全阻止,这两种抑制剂都是肌浆网Ca2+释放的抑制剂,或细胞外Ca2+的遗漏。虽然PAO治疗(.gtoreq。20 .mu。解析:选c。80%的3-MG转运增加是由胰岛素引起的,它只导致了大约1。缺氧或收缩活动对3-MG转运的刺激抑制50%。PAO处理(40 .亩)已经受到胰岛素、收缩活动或缺氧最大刺激的肌肉的M)并没有逆转3-MG运输的增强速率。这些数据表明,与肌肉收缩或缺氧相比,邻近巯基在胰岛素激活葡萄糖运输中起着更大的作用。PAO抑制葡萄糖转运的刺激,但在刺激后不影响葡萄糖转运,这一发现提供了证据,表明邻基巯基参与了肌肉中葡萄糖转运激活的途径,但不参与葡萄糖转运机制本身。
The trivalent arsenical phenylarsine oxide (PAO) inhibits insulin-stimulated glucose transport in adipocytes and skeletal muscle through direct interactions with vicinal sulfhydryls. In muscle, glucose transport is also activated by contractile activity and hypoxia. It was therefore the purpose of the present study to investigate whether vicinal sulfhydryls are involved in the stimulation of glucose transport activity in the isolated rat epitrochlearis muscle by hypoxia or contractions. PAO (>5 .mu.M) caused a twofold increase in rate of transport of the nonmetabolizable glucose analogue 3-O-methylglucose (3-MG) that was completely prevented by cytochalasin B, the vicinal dithiol dimercaptopropanol, dantrolene, or 9-aminoacridine, both inhibitors of sarcoplasmic reticulum Ca2+ release, or omission of extracellular Ca2+. Although PAO treatment (.gtoreq.20 .mu.M) prevented .apprx.80% of the increase in 3-MG transport caused by insulin, it resulted in only a .apprx.50% inhibition of the stimulation of 3-MG transport by either hypoxia or contractile activity. PAO treatment (40 .mu.M) of muscles already maximally stimulated by insulin, contractile activity, or hypoxia did not reverse the enhanced rate of 3-MG transport. These data suggest that vicinal sulfhydryls play a greater role in the activation of glucose transport by insulin than by muscle contractions or hypoxia. The finding that PAO inhibits the stimulation of glucose transport, but does not affect glucose transport after it has been stimulated, provides evidence that vicinal sulfhydryls are involved in the pathways for glucose transport activation in muscle, but not in the glucose transport mechanism itself.