No evidence of direct association between GLUT4 and glycogen in human skeletal muscle.

Robyn M Murphy,Barnaby P Frankish,David Stapleton,Andrew Garnham,Marcelo Flores-Opazo,Mark Hargreaves

doi:10.14814/phy2.13917

Abstract

Previous studies have demonstrated that exercise increases whole body and skeletal muscle insulin sensitivity that is linked with increased GLUT4 at the plasma membrane following insulin stimulation and associated with muscle glycogen depletion. To assess the potential direct association between muscle glycogen and GLUT4, seven untrained, male subjects exercised for 60 min at ~75% VO2 peak, with muscle samples obtained by percutaneous needle biopsy immediately before and after exercise. Exercise reduced muscle glycogen content by ~43%. An ultracentrifugation protocol resulted in a ~2‐3‐fold enriched glycogen fraction from muscle samples for analysis. Total GLUT4 content was unaltered by exercise and we were unable to detect any GLUT4 in glycogen fractions, either with or without amylase treatment. In skinned muscle fiber segments, there was very little, if any, GLUT4 detected in wash solutions, except following exposure to 1% Triton X‐100. Amylase treatment of single fibers did not increase GLUT4 in the wash solution and there were no differences in GLUT4 content between fibers obtained before or after exercise for any of the wash treatments. Our results indicate no direct association between GLUT4 and glycogen in human skeletal muscle, before or after exercise, and suggest that alterations in GLUT4 translocation associated with exercise‐induced muscle glycogen depletion are mediated via other mechanisms.

Highlights

It is well recognized from studies in rodents and humans that exercise increases insulin-stimulated glucose uptake in skeletal muscle (Richter et al 1982, 1989; Cartee and Holloszy 1990; Wojtaszewski et al 2000)
Total GLUT4 content was unaltered by exercise and we were unable to detect any GLUT4 in glycogen fractions, either with or without amylase treatment (Fig. 1)
Using two different analytical approaches, our results suggest that there is no direct association between GLUT4containing vesicles and glycogen in human skeletal muscle

Summary

Introduction

It is well recognized from studies in rodents and humans that exercise increases insulin-stimulated glucose uptake in skeletal muscle (Richter et al 1982, 1989; Cartee and Holloszy 1990; Wojtaszewski et al 2000). This is associated with muscle glycogen depletion during exercise (Bogardus et al 1983; Ivy et al 1985) and enhanced GLUT4 translocation to the plasma membrane with insulin stimulation in the post-exercise period (Hansen et al 1998).

Methods

Results

Conclusion