Physical inactivity affects skeletal muscle insulin signaling in a birth weight-dependent manner

Brynjulf Mortensen1, Martin Friedrichsen1, Nicoline R Andersen2

  • 1Steno Diabetes Center, Gentofte, Denmark; Molecular Physiology Group, The August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen.

Insights

Physical inactivity may reveal underlying insulin signaling defects in low birth weight (LBW) individuals. While bed rest caused similar insulin resistance in LBW and normal birth weight (NBW) groups, LBW subjects showed impaired muscle insulin signaling.

Area of Science:

  • Endocrinology
  • Metabolic Research
  • Exercise Physiology

Background:

  • Low birth weight (LBW) is a risk factor for metabolic disorders.
  • The impact of physical inactivity on insulin and AMPK signaling in LBW individuals remains unclear.

Purpose of the Study:

  • To investigate if physical inactivity unmasks defects in insulin and AMPK signaling pathways in low birth weight (LBW) subjects.
  • To compare the effects of bed rest on insulin sensitivity and signaling between LBW and normal birth weight (NBW) individuals.

Main Methods:

  • Twenty LBW and 20 NBW subjects underwent a 9-day bed rest protocol.
  • Euglycemic-hyperinsulinemic clamp and skeletal muscle biopsies were performed pre and post bed rest.
  • Western blotting analyzed Akt, AS160, GLUT4, and AMPK signaling pathways.

Main Results:

  • Both LBW and NBW groups exhibited similar reductions in peripheral insulin action post bed rest.
  • Insulin and AMPK signaling remained unaffected by bed rest in NBW subjects.
  • LBW subjects displayed decreased insulin-stimulated Akt phosphorylation and altered AMPK expression post bed rest, with lower insulin response in AS160 phosphorylation.

Conclusions:

  • Bed rest-induced insulin resistance is not solely explained by impaired muscle insulin or AMPK signaling in either group.
  • Reduced muscle insulin signaling in LBW subjects post bed rest, despite similar insulin resistance, suggests a potential heightened risk for type 2 diabetes with physical inactivity.
Abstract

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