Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.
Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.
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DOI：
10.1371/journal.pone.0009600
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发表时间：
2010-03-09
期刊：
影响因子：
3.7
通讯作者：
Ryu SH
中科院分区：
文献类型：
--
作者：
Kim JH;Park JM;Yea K;Kim HW;Suh PG;Ryu SH
葡萄糖稳态通过肝葡萄糖产生和外周葡萄糖利用之间的平衡来维持。在骨骼肌细胞中，葡萄糖利用主要受葡萄糖摄取调节。细胞能量的剥夺会诱导调节蛋白的激活，从而诱导葡萄糖的摄取。已知 AMP 激活蛋白激酶 (AMPK) 在能量平衡调节中发挥重要作用。然而，与 AMPK 介导的葡萄糖摄取控制相关的机制尚未阐明。在这里，我们发现在葡萄糖剥夺条件下，AMPK 诱导的磷脂酶 D1 (PLD1) 激活是肌肉细胞摄取 14C-葡萄糖所必需的。葡萄糖剥夺显着增强了 PLD1 活性，而不是 PLD2 活性。 AMPK 野生型 (WT) 刺激 PLD 活性，而 AMPK 显性阴性 (DN) 则抑制它。 AMPK 通过 Ser-505 的磷酸化来调节 PLD1 活性，并且这种磷酸化会因 AMP 的存在而增强。此外，与 PLD1-WT 相比，PLD1-S505Q（一种磷酸化缺陷突变体）对葡萄糖剥夺的反应没有表现出活性变化，并且 14C-葡萄糖摄取没有表现出显着增加。综上所述，这些结果表明 PLD1 的磷酸化对于 14C-葡萄糖摄取的调节很重要。此外，AMPK 诱导的 PLD1 激活会通过形成磷脂酸 (PA)（PLD 的产物）来刺激细胞外信号调节激酶 (ERK)。 ERK 药理学抑制剂 PD98059 和 PLD 抑制剂 1-BtOH 均可减弱肌肉细胞对 14C-葡萄糖的摄取。最后，由葡萄糖剥夺或氨基咪唑甲酰胺核糖核苷酸（AICAR；AMPK 激活剂）引起的细胞外应激通过 AMPK 介导的 PLD1 激活通过 ERK 刺激调节 14C-葡萄糖摄取和细胞表面葡萄糖转运 (GLUT) 4。这些结果表明，AMPK 介导的 PLD1 激活是通过 ERK 刺激摄取 14C-葡萄糖所必需的。我们认为 AMPK 介导的 PLD1 通路可能为理解葡萄糖摄取机制提供重要线索。
Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK) is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated. Here, we found that AMPK-induced phospholipase D1 (PLD1) activation is required for 14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT) stimulates PLD activity, while AMPK-dominant negative (DN) inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in 14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of 14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK) is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA), which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate 14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator) regulate 14C-glucose uptake and cell surface glucose transport (GLUT) 4 through ERK stimulation by AMPK-mediated PLD1 activation. These results suggest that AMPK-mediated PLD1 activation is required for 14C-glucose uptake through ERK stimulation. We propose that the AMPK-mediated PLD1 pathway may provide crucial clues to understanding the mechanisms involved in glucose uptake.
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影响因子：
3.3
作者：
Du, GW;Huang, P;Frohman, MA
通讯作者：
Frohman, MA
影响因子：
3.3
作者：
Freyberg, Z;Sweeney, D;Shields, D
通讯作者：
Shields, D
影响因子：
4.8
作者：
Kim, Jung Hwan;Kim, Hyun-Wook;Ryu, Sung Ho
通讯作者：
Ryu, Sung Ho
影响因子：
5.3
作者：
Kim, JH;Kim, JH;Ryu, SH
通讯作者：
Ryu, SH
DOI：
10.1006/bbrc.2001.5544
发表时间：
2001-09-14
影响因子：
3.1
作者：
Choi, SL;Kim, SJ;Ha, J
通讯作者：
Ha, J