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Fiber type-selective exercise effects on AS160 phosphorylation.

Haiyan Wang1, Edward B Arias1, Kentaro Oki1

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|March 6, 2019
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Exercise enhances insulin sensitivity by increasing Akt substrate of 160 kDa (AS160) phosphorylation in specific muscle fiber types, independent of GLUT4 changes. This improves insulin-stimulated glucose uptake (ISGU) post-exercise.

Keywords:
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Area of Science:

  • Exercise physiology
  • Skeletal muscle metabolism
  • Insulin signaling

Background:

  • Postexercise elevation in insulin-stimulated glucose uptake (ISGU) is linked to increased insulin-stimulated Akt substrate of 160 kDa (AS160) phosphorylation (pAS160).
  • Skeletal muscle heterogeneity necessitates fiber type-specific analysis of exercise effects on ISGU and pAS160.

Purpose of the Study:

  • To determine if exercise-induced increases in pAS160 occur in a fiber type-selective manner corresponding to previously observed ISGU.
  • To investigate the relationship between fiber type-specific pAS160 and ISGU post-exercise.

Main Methods:

  • Rats were studied immediately postexercise (IPEX) and 3.5 hours postexercise (3.5hPEX), with time-matched sedentary controls.
  • Myofibers were analyzed for fiber type (myosin heavy chain isoforms), pAS160, and GLUT4 protein abundance.
  • Insulin stimulation was performed on isolated muscles from the 3.5hPEX experiment.

Main Results:

  • Exercise recruited all fiber types, indicated by increased phosphorylation of AMP-activated kinase substrates.
  • Insulin-stimulated pAS160 (Thr642 and Ser704) was elevated in type I, IIA, IIB, and IIBX fibers at 3.5hPEX compared to sedentary controls.
  • No significant changes in GLUT4 protein abundance were observed in any fiber type at 3.5hPEX.

Conclusions:

  • Enhanced insulin-stimulated AS160 phosphorylation is fiber type-specific and linked to elevated ISGU post-exercise.
  • This mechanism contributes to exercise-induced insulin sensitization independently of alterations in GLUT4 expression.