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

运动是骨骼肌中葡萄糖代谢的潜在刺激剂。 AMPK是一种由催化α和调节性β和γ亚基组成的异三聚体蛋白，并且会因骨骼肌运动而迅速激活。本研究的主要目的是确定合同刺激的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个不同的α同工型：α1和α2。超生理收缩，例如通过肌肉刺激的四核收缩，都激活了α1和α2，但是中等强度的运动，例如在大鼠骨骼肌中选择性地激活的α2跑步机。与胰岛素独立的葡萄糖转运活性并行，以运动强度和持续时间依赖性方式增加了α2活性。此外，对α2的药物抑制显着抑制了大鼠肌肉在体外的合同刺激的葡萄糖转运。类似于动物肌肉的观察结果，结束……更多的尿液运动（= 70％vo2max）被证明会激活刺激α2的葡萄糖转运，但在人骨骼肌中却没有α1。通过腹膜内或皮下注射AICAR激活的小鼠骨骼肌中的葡萄糖转运的药理α-2激活，这在响应现代强度运动的范围内也相似。此外，类似于慢性运动训练的作用，反复注射AICAR 4-7天显着增加了小鼠骨骼肌中葡萄糖转运蛋白glut4。这些结果表明，AMPKα2是一种信号传导中间体，导致运动刺激的葡萄糖转运和GLUT4表达，而AMPK似乎在骨骼肌中运动刺激的糖原代谢中并不重要。当大鼠肌肉在存在噻唑烷二酮的情况下孵育时，处方广泛的抗糖尿病试剂时，α2与胰岛素独立的葡萄糖转运活性并联时显着刺激。除了提高胰岛素敏感性的常规作用外，噻唑烷二酮还可能通过AMPK依赖性机制对骨骼肌葡萄糖转运产生运动样作用。较少的

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: "5' AMP-activated protein kinaseを基準とした糖代謝活性化のための新しい動処方の研究"平成11年度研究報告書 (財)総合健康推進財団. 93-105 (2002)

Tatsuya Hayashi：“基于 5 AMP 激活蛋白激酶的激活葡萄糖代谢的新动态方案的研究”1999 年研究报告，一般健康促进基金会 93-105 (2002)。