Exercise-Induced Improvement in Insulin-Stimulated Glucose Uptake by Rat Skeletal Muscle Is Absent in Male AS160-Knockout Rats, Partially Restored by Muscle Expression of Phosphomutated AS160, and Fully Restored by Muscle Expression of Wild-Type AS160

被引:11
|
作者
Zheng, Amy [1 ]
Arias, Edward B. [1 ]
Wang, Haiyan [1 ]
Kwak, Seong Eun [1 ]
Pan, Xiufang [2 ]
Duan, Dongsheng [2 ,3 ,4 ,5 ]
Cartee, Gregory D. [1 ,6 ,7 ]
机构
[1] Univ Michigan, Sch Kinesiol, Muscle Biol Lab, Ann Arbor, MI 48109 USA
[2] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO USA
[3] Univ Missouri, Dept Biomed Sci, Coll Vet Med, Columbia, MO USA
[4] Univ Missouri, Sch Med, Dept Neurol, Columbia, MO USA
[5] Univ Missouri, Dept Biomed Biol & Chem Engn, Coll Engn, Columbia, MO USA
[6] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
[7] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA
基金
美国国家卫生研究院;
关键词
AKT SUBSTRATE; PHOSPHORYLATION; TRANSPORT; TBC1D1; SENSITIVITY; GLUT4; RESISTANCE; INCREASES; KINASE; MICE;
D O I
10.2337/db21-0601
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
One exercise session can elevate insulin-stimulated glucose uptake (ISGU) in skeletal muscle, but the mechanisms remain elusive. Circumstantial evidence suggests a role for Akt substrate of 160 kDa (AS160 or TBC1D4). We used genetic approaches to rigorously test this idea. The initial experiment evaluated the role of AS160 in postexercise increase in ISGU using muscles from male wild-type (WT) and AS160-knockout (KO) rats. The next experiment used AS160-KO rats with an adeno-associated virus (AAV) approach to determine if rescuing muscle AS160 deficiency could restore the ability of exercise to improve ISGU. The third experiment tested if eliminating the muscle GLUT4 deficit in AS160-KO rats via AAV-delivered GLUT4 would enable postexercise enhancement of ISGU. The final experiment used AS160-KO rats and AAV delivery of AS160 mutated to prevent phosphorylation of Ser588, Thr642, and Ser704 to evaluate their role in postexercise ISGU. We discovered the following: 1) AS160 expression was essential for postexercise increase in ISGU; 2) rescuing muscle AS160 expression of AS160-KO rats restored postexercise enhancement of ISGU; 3) restoring GLUT4 expression in AS160-KO muscle did not rescue the postexercise increase in ISGU; and 4) although AS160 phosphorylation on three key sites was not required for postexercise elevation in ISGU, it was essential for the full exercise effect.
引用
收藏
页码:219 / 232
页数:14
相关论文
共 17 条
  • [1] Rapid Reversal of Insulin-Stimulated AS160 Phosphorylation in Rat Skeletal Muscle after Insulin Exposure
    Sharma, N.
    Arias, E. B.
    Cartee, G. D.
    PHYSIOLOGICAL RESEARCH, 2010, 59 (01) : 71 - 78
  • [2] AS160 expression, but not AS160 Serine-588, Threonine-642, and Serine-704 phosphorylation, is essential for elevated insulin-stimulated glucose uptake by skeletal muscle from female rats after acute exercise
    Wang, Haiyan
    Zheng, Amy
    Arias, Edward B.
    Kwak, Seong Eun
    Pan, Xiufang
    Duan, Dongsheng
    Cartee, Gregory D.
    FASEB JOURNAL, 2023, 37 (07): : e23021
  • [3] AS160 Expression, but Not AS160 Serine-588, Threonine-642, and Serine-704 Phosphorylation, Is Essential for Elevated Insulin-Stimulated Glucose Uptake by Skeletal Muscle from Female Rats after Acute Exercise
    Wang, Haiyan
    Zheng, Amy
    Arias, Edward B.
    Kwak, Seongeun
    Pan, Xiufang
    Yue, Yongping
    Duan, Dongsheng
    Cartee, Gregory D.
    DIABETES, 2023, 72
  • [4] Calmodulin-binding domain of AS160 regulates contraction- but not insulin-stimulated glucose uptake in skeletal muscle
    Kramer, Henning F.
    Taylor, Eric B.
    Witczak, Carol A.
    Fujii, Nobuharu
    Hirshman, Michael F.
    Goodyear, Laurie J.
    DIABETES, 2007, 56 (12) : 2854 - 2862
  • [5] AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle
    Kramer, Henning F.
    Witczak, Carol A.
    Taylor, Eric B.
    Fujii, Nobuharu
    Hirshman, Michael F.
    Goodyear, Laurie J.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (42) : 31478 - 31485
  • [6] Fiber type-specific effects of acute exercise on insulin-stimulated AS160 phosphorylation in insulin-resistant rat skeletal muscle
    Pataky, Mark W.
    Van Acker, Sydney L.
    Dhingra, Rhea
    Freeburg, Marina M.
    Arias, Edward B.
    Oki, Kentaro
    Wang, Haiyan
    Treebak, Jonas T.
    Cartee, Gregory D.
    AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2019, 317 (06): : E984 - E998
  • [7] Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects
    Karlsson, HKR
    Zierath, JR
    Kane, S
    Krook, A
    Lienhard, GE
    Wallberg-Henriksson, H
    DIABETES, 2005, 54 (06) : 1692 - 1697
  • [8] Postexercise Improvement in Insulin-Stimulated Glucose Uptake Occurs Concomitant With Greater AS160 Phosphorylation in Muscle From Normal and Insulin-Resistant Rats
    Castorena, Carlos M.
    Arias, Edward B.
    Sharma, Naveen
    Cartee, Gregory D.
    DIABETES, 2014, 63 (07) : 2297 - 2308
  • [9] Exercise effects on γ3-AMPK activity, phosphorylation of Akt2 and AS160, and insulin-stimulated glucose uptake in insulin-resistant rat skeletal muscle
    Pataky, Mark W.
    Arias, Edward B.
    Wang, Haiyan
    Zheng, Xiaohua
    Cartee, Gregory D.
    JOURNAL OF APPLIED PHYSIOLOGY, 2020, 128 (02) : 410 - 421
  • [10] Postexercise improvement in glucose uptake occurs concomitant with greater γ3-AMPK activation and AS160 phosphorylation in rat skeletal muscle
    Wang, Haiyan
    Arias, Edward B.
    Pataky, Mark W.
    Goodyear, Laurie J.
    Cartee, Gregory D.
    AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2018, 315 (05): : E859 - E871