Effects of Exercise-Induced Activation of 5'AMP-Activated Protein Kinase (AMPK) on Glucose Metabolism in Skeletal Muscle

运动诱导的 5AMP 激活蛋白激酶 (AMPK) 激活对骨骼肌葡萄糖代谢的影响

• 批准号: 12671112
• 负责人: HAYASHI Tatsuya
• 金额: $ 2.18万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671112/
• 关键词: AMP kinase; skeletal muscle; glucose metabolism; exercise; muscle contraction; signal transduction; glucose transport; glycogen

Exercise is a potent stimulator of glucose metabolism in skeletal muscle. AMPK is a heterotrimeric protein consisting of catalytic α and regulatory β and γ subunits, and is rapidly activated in response to exercise in skeletal muscle. The main purpose of the present study was to determine if contraction-stimulated AMPK plays a role in regulating muscle glucose metabolism. Mammalian skeletal muscle expresses two distinct α isoforms: α1 and α2. Supraphysiological contraction, such as tetanic contraction by electromyostimulation, activated both α1 and α2, but moderate-intensity exercise such as treadmill running selectively activated α2 in rat skeletal muscle. α2 activity was increased in an exercise intensity- and duration-dependent manner, in parallel with insulin-independent glucose transport activity. Furthermore, pharmacological inhibition of α2 significantly inhibited contraction-stimulated glucose transport in rat muscles in vitro. Similar to the observations of animal muscles, end … More urance exercise (= 70 %VO2max) that had been shown to activate glucose transport stimulated α2, but not α1 in human skeletal muscle. Pharmacological α-2 activation by intraperitoneal or subcutaneous injection of AICAR activated glucose transport in mouse skeletal muscle, to a similar extent that was achieved in response to moderate-intensity exercise. In addition, similar to the effect of chronic exercise training, repeated injections of AICAR for 4-7 days significantly increased glucose transporter GLUT4 in mouse skeletal muscle. These results suggest that AMPKα2 is a signaling intermediary leading to exercise-stimulated glucose transport and GLUT4 expression, while AMPK does not seem to play a major role in exercise-stimulated glycogen metabolism in skeletal muscle. When rat muscles were incubated in the presence of thiazolidinediones, widely prescribed antidiabetic reagents, α2 was significantly stimulated in parallel with insulin-independent glucose transport activity. In addition to the conventional effect of increasing insulin sensitivity, thiazolidinediones may have an exercise-like effect on skeletal muscle glucose transport via AMPK-dependent mechanism. Less

运动是骨骼肌糖代谢的有力刺激因素。AMPK是一种由催化α、调节β和γ亚基组成的异三聚体蛋白，在骨骼肌中运动后被迅速激活。本研究的主要目的是确定收缩刺激的AMPK是否在调节肌肉葡萄糖代谢中起作用。哺乳动物骨骼肌表达两种不同的α亚型：α1和α2。超生理收缩，如肌肉刺激的强直性收缩，激活α1和α2，而中等强度运动，如跑步机跑，选择性地激活大鼠骨骼肌中的α2。α-2活性以运动强度和持续时间依赖的方式增加，与胰岛素非依赖性葡萄糖转运活动平行。此外，药物抑制α-2可显著抑制收缩刺激的大鼠肌肉葡萄糖转运。与对动物肌肉的观察类似，End…更多的耐力运动(=70%Vo2max)已被证明能激活葡萄糖转运，刺激人骨骼肌的α-2，但不能刺激α-1。通过腹膜内或皮下注射AICAR的药理学α-2激活激活了小鼠骨骼肌中的葡萄糖运输，其程度与中等强度运动的反应相似。此外，与慢性运动训练的效果相似，重复注射AICAR 4-7天可显著增加小鼠骨骼肌中葡萄糖转运体GLUT4的含量。这些结果表明，AMPKGLUT2是导致运动刺激的葡萄糖转运和α表达的信号媒介，而AMPKGLUT4在运动刺激的骨骼肌糖原代谢中似乎并不起主要作用。当大鼠肌肉与噻唑烷二酮(一种广泛使用的抗糖尿病试剂)孵育时，α-2被显著地刺激，同时具有胰岛素非依赖性的葡萄糖转运活性。除了增加胰岛素敏感性的传统作用外，噻唑烷二酮类化合物可能通过AMPK依赖机制对骨骼肌葡萄糖运输具有运动样作用。较少

项目成果

林 達也: "5' AMP-activated protein kinaseを基準とした糖代謝改善のための新しい運動プログラムの開発"健康医科学研究助成論文集. 16. 132-141 (2001)

Tatsuya Hayashi：“基于 5 AMP 激活蛋白激酶改善葡萄糖代谢的新运动计划的开发”健康与医学科学研究资助杂志 16. 132-141 (2001)。

Nakano M.: "Alpha 2 isoform-specific activation of 5'AMP-activated protein kinase (AMPK) stimulates glucose transport and GLUT4 expression in mouse skeletal muscle"Diabetes. 50(Suppl.2). A224 (2001)

Nakano M.：“5AMP 激活蛋白激酶 (AMPK) 的 Alpha 2 同种型特异性激活刺激小鼠骨骼肌中的葡萄糖转运和 GLUT4 表达”糖尿病。

Yonemitsu S.: "Thiazolidinediones directly stimulate glucose transport via insulin-independent mechanism in rat skeletal muscle"Diabetes. 50(Suppl.2). A273 (2001)

Yonemitsu S.：“噻唑烷二酮通过大鼠骨骼肌中的胰岛素独立机制直接刺激葡萄糖转运”糖尿病。

林 達也: "運動による糖輸送活性化の分子機構"最新医学. 55. 1078-1083 (2000)

Tatsuya Hayashi：“运动激活糖转运的分子机制”现代医学 55. 1078-1083 (2000)。

林 達也: "運動による糖代謝活性化の分子機構に基づいた新しい運動プログラムの開発"デサントスポーツ科学. 22. 31-40 (2001)

Tatsuya Hayashi：“基于运动激活葡萄糖代谢的分子机制开发新的运动计划”DESCENTE Sports Science 22. 31-40 (2001)。