Glycogenin protein and mRNA expression in response to changing glycogen concentration in exercise and recovery

Abstract

Wilson RJ, Gusba JE, Robinson DL, Graham TE. Glycogenin protein and mRNA expression in response to changing glycogen concentration in exercise and recovery. Am J Physiol Endocrinol Metab 292: E1815-E1822, 2007. First published February 20, 2007 doi:10.1152/ajpendo.00598.2006 is essential for the formation of a glycogen granule; however, rarely has it been studied when glycogen concentration changes in exercise and recovery. It is unclear whether GN-1 is degraded or is liberated and exists as apoprotein (apo)-GN-1 (unglycosylated). To examine this, we measured GN-1 protein and mRNA level at rest, at exhaustion (EXH), and during 5 h of recovery in which the rate of glycogen restoration was influenced by carbohydrate (CHO) provision. Ten males cycled (65% V O2 max) to volitional EXH (117.8 Ϯ 4.2 min) on two separate occasions. Subjects were administered carbohydrate (CHO; 1 g⅐ kg Ϫ1 ⅐ h Ϫ1 Gatorlode) or water [placebo (PL)] during 5 h of recovery. Muscle biopsies were taken at rest, at EXH, and following 30, 60, 120, and 300 min of recovery. At EXH, total glycogen concentration was reduced (P Ͻ 0.05). However, GN-1 protein and mRNA content did not change. By 5 h of recovery, glycogen was resynthesized to ϳ60% of rest in the CHO trial and remained unchanged in the PL trial. GN-1 protein and mRNA level did not increase during recovery in either trial. We observed modest amounts of apo-GN-1 at EXH, suggesting complete degradation of some granules. These data suggest that GN-1 is conserved, possibly as very small, or nascent, granules when glycogen concentration is low. This would provide the ability to rapidly restore glycogen during early recovery. skeletal muscle; carbohydrate; exhaustion; resynthesis; recovery THE SKELETAL MUSCLE ISOFORM of the autoglycosylating protein glycogenin-1 (GN-1) binds a chain of 5-13 glucose molecules (3, 23) at a specific tyrosine residue (Y194) (7,26,29). This is a critical, fundamental step in the formation of a glycogen granule. The covalently associated protein-carbohydrate "primer" serves as a substrate for the catalyzed formation of glycogen by glycogen synthase in concert with branching enzyme (16,25,30).Although it is appreciated that GN-1 is essential for the formation of a glycogen granule, its regulation has rarely been studied in human tissue, and its fate is unknown in circumstances where glycogen stores decrease. Work with cultured myotubes (10) suggests that some glycogen granules may be completely catabolized when glycogen stores are decreased. Under these circumstances, it is unknown whether the protein is degraded or is liberated as apoprotein (apo)-GN-1 (i.e., unglucosylated) and/or is translocated. Presumably, GN-1 would have to be available rapidly when glycogen stores are restored. Examinations of GN-1 in human muscle have focused predominantly on "activity" and mRNA during exercise and recovery. There are reports that GN-1 mRNA increases approximately twofold during prolonged exercise and/or the early part of recovery (14,27,28). Surprisingly, the effects of a ca...

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“…For example, we do not know what happens to GN as granules are degraded; is it degraded, inactivated or remains in an active form? Using a human exercise model, work from our laboratory suggests that GN may not be degraded, but rather is for the most part conserved in smaller glycogen granules when glycogen content is significantly reduced (Wilson et al. 2007), thereby providing substrate for GS to resynthesize glycogen during recovery.…”

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