AMPK is indispensable for overload-induced muscle glucose uptake and glycogenesis but dispensable for inducing hypertrophy in mice

FASEB J. 2021 Apr;35(4):e21459. doi: 10.1096/fj.202002164R.

Abstract

Chronic muscle loading (overload) induces skeletal muscles to undergo hypertrophy and to increase glucose uptake. Although AMP-activated protein kinase (AMPK) reportedly serves as a negative regulator of hypertrophy and a positive regulator of glucose uptake, its role in overload-induced skeletal muscle hypertrophy and glucose uptake is unclear. This study aimed to determine whether AMPK regulates overload-induced hypertrophy and glucose uptake in skeletal muscles. To this end, skeletal muscle overload was induced through unilateral synergist ablations in wild-type (WT) and transgenic mice, expressing the dominant-negative mutation of AMPK (AMPK-DN). After 14 days, parameters, including muscle fiber cross-sectional area (CSA), glycogen level, and in vivo [3 H]-2-deoxy-D-glucose uptake, were assessed. No significant difference was observed in body weight or blood glucose level between the WT and AMPK-DN mice. However, the 14-day muscle overload activated the AMPK pathway in WT mice skeletal muscle, whereas this response was impaired in the AMPK-DN mice. Despite a normal CSA gain in each fiber type, the AMPK-DN mice demonstrated a significant impairment of overload-induced muscle glucose uptake and glycogenesis, compared to WT mice. Moreover, 14-day overload-induced changes in GLUT4 and HKII expression levels were reduced in AMPK-DN mice, compared to WT mice. This study demonstrated that AMPK activation is indispensable for overload-induced muscle glucose uptake and glycogenesis; however, it is dispensable for the induction of hypertrophy in AMPK-DN mice. Furthermore, the AMPK/GLUT4 and HKII axes may regulate overload-induced muscle glucose uptake and glycogenesis.

Keywords: AMP-activated protein kinase; functional overload; glucose uptake; hypertrophy; skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Glucose / metabolism*
  • Glycogen / metabolism
  • Hypertrophy / metabolism*
  • Mice, Transgenic
  • Muscle, Skeletal / metabolism
  • Muscles / metabolism*
  • Protein Serine-Threonine Kinases / metabolism

Substances

  • Glycogen
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Glucose