Glueose autoregulates its uptake in skeletal muscle - Involvement of AMP-activated protein kinase
Glueose autoregulates its uptake in skeletal muscle - Involvement of AMP-activated protein kinase
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DOI：
10.2337/diabetes.52.7.1635
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发表时间：
2003-07-01
期刊：
影响因子：
7.7
通讯作者：
Ruderman, NB
中科院分区：
文献类型：
--
作者：
Itani, SI;Saha, AK;Ruderman, NB
预先暴露于低浓度的葡萄糖会上调葡萄糖转运到骨骼肌中，而暴露于高浓度的葡萄糖则具有相反的效果。这种自动调节过程独立于胰岛素而发生，其运作机制尚不完全清楚。能量感应酶 AMP 激活蛋白激酶 (AMPK) 的激活已被证明可以增加不依赖胰岛素的葡萄糖转运到骨骼肌中，以响应运动和缺氧等刺激。在本研究中，我们检查了 AMPK 是否也可以介导葡萄糖自动调节。在含有 0、3、6 或 25 mmol/l 葡萄糖的培养基中预温育 4 It 后，在培养的大鼠趾长伸肌中评估 AMPK α2 同工型的活性和 2-脱氧葡萄糖摄取。主要调查结果如下。首先，在未添加葡萄糖的情况下培养的肌肉中，AMPK 活性最高，并且随着葡萄糖浓度的增加而降低。与这些发现一致，随着培养基葡萄糖浓度的升高，丙二酰辅酶A的浓度增加，并且丝氨酸79处的乙酰辅酶A羧化酶磷酸化降低。其次，在较高葡萄糖浓度下 AMPK 活性的降低与葡萄糖转运（2-脱氧葡萄糖摄取）的降低密切相关，在随后的 6 mmol/l 葡萄糖孵育 20 分钟期间进行测量（r(2) = 0.93，P < 0.001）。第三，较高葡萄糖浓度下 AMPK 活性的降低与全组织磷酸肌酸或腺嘌呤核苷酸浓度的变化无关。然而，根据乳酸释放的估计，它确实与糖酵解速率的增加相关。结果表明，葡萄糖通过涉及 AMPK 的机制自动调节自身向骨骼肌的转运。他们还表明，这种自动调节机制与磷酸肌酸 ATP 或 AMP 全组织浓度的变化并不平行，但他们提出了这些化合物的细胞质库的变化发挥调节作用的可能性。
Preexposure to a low concentration of glucose upregulates glucose transport into skeletal muscle, whereas exposure to a high concentration of glucose has the opposite effect. This autoregulatory process occurs independently of insulin, and the mechanism by which it operates is incompletely understood. Activation of the energy-sensing enzyme AMP-activated protein kinase (AMPK) has been shown to increase insulin-independent glucose transport into skeletal muscle in response to such stimuli as exercise and hypoxia. In the present study, we examined whether AMPK could also mediate glucose autoregulation. The activity of the alpha2 isoform of AMPK and 2-deoxyglucose uptake were assessed in incubated rat extensor digitorum longus muscle after preincubation for 4 It in media containing 0, 3, 6, or 25 mmol/l glucose. The principal findings were as follows. First, AMPK activity was highest in muscles incubated with no added glucose, and it decreased as the concentration of glucose was increased. In keeping with these findings, the concentration of malonyl CoA was increased, and acetyl CoA carboxylase phosphorylation at serine 79 was decreased as the medium glucose concentration was raised. Second, decreases in AMPK activity at the higher glucose concentrations correlated closely with decreases in glucose transport (2-deoxyglucose uptake), measured during a subsequent 20-min incubation at 6 mmol/l glucose (r(2) = 0.93, P < 0.001). Third, the decrease in AMPK activity at the higher glucose concentrations was not associated with changes in whole-tissue concentrations of creatine phosphate or adenine nucleotides; however, it did correlate with increases in the rate of glycolysis, as estimated by lactate release. The results suggest that glucose autoregulates its own transport into skeletal muscle by a mechanism involving AMPK. They also suggest that this autoregulatory mechanism is not paralleled by changes in whole-tissue concentrations of creatine phosphate ATP, or AMP, but they leave open the possibility that alterations in a cytosolic pool of these compounds play a regulatory role.