Article

Role of 5'AMP-activated protein kinase in glycogen synthase activity and glucose utilization: insights from patients with McArdle's disease.

Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Denmark.
The Journal of Physiology (impact factor: 4.72). 06/2002; 541(Pt 3):979-89. pp.979-89
Source: PubMed

ABSTRACT It has been suggested that 5'AMP-activated protein kinase (AMPK) is involved in the regulation of glucose and glycogen metabolism in skeletal muscle. We used patients with chronic high muscle glycogen stores and deficient glycogenolysis (McArdle's disease) as a model to address this issue. Six McArdle patients were compared with control subjects during exercise. Muscle alpha2AMPK activity increased in McArdle patients (from 1.3 +/- 0.2 to 1.9 +/- 0.2 pmol min(-1) mg(-1), P = 0.05) but not in control subjects (from 1.0 +/- 0.1 to 1.3 +/- 0.3 pmol min(-1) mg(-1)). Exercise-induced phosphorylation of the in vivo AMPK substrate acetyl CoA carboxylase (ACCbeta; Ser(221)) was higher (P < 0.01) in McArdle patients than in control subjects (18 +/- 3 vs. 10 +/- 1 arbitrary units). Exercise-induced whole-body glucose utilization was also higher in McArdle patients than in control subjects (P < 0.05). No correlation between individual AMPK or ACCbeta values and glucose utilization was observed. Glycogen synthase (GS) activity was decreased in McArdle patients from 11 +/- 1.3 to 5 +/- 1.2 % (P < 0.05) and increased in control subjects from 19 +/- 1.6 to 23 +/- 2.3 % (P < 0.05) in response to exercise. This was not associated with activity changes of GS kinase 3 or protein phosphatase 1, but the changes in GS activity could be due to changes in activity of AMPK or protein kinase A (PKA) as a negative correlation between either ACCbeta phosphorylation (Ser(221)) or plasma adrenaline and GS activity was observed. These findings suggest that GS activity is increased by glycogen breakdown and decreased by AMPK and possibly PKA activation and that the resultant GS activity depends on the relative strengths of the various stimuli. Furthermore, AMPK may be involved in the regulation of glucose utilization during exercise in humans, although the lack of correlation between individual AMPK activity or ACCbeta phosphorylation (Ser(221)) values and individual glucose utilization during exercise implies that AMPK may not be an essential regulator.

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

10 +/- 1 arbitrary units
 
5'AMP-activated protein kinase
 
ACCbeta phosphorylation
 
ACCbeta values
 
essential regulator
 
Exercise-induced phosphorylation
 
Exercise-induced whole-body glucose utilization
 
glycogen metabolism
 
GS activity
 
GS kinase 3
 
individual AMPK
 
individual AMPK activity
 
McArdle patients
 
McArdle's disease
 
Muscle alpha2AMPK activity
 
negative correlation
 
protein phosphatase 1
 
relative strengths
 
resultant GS activity
 
vivo AMPK substrate acetyl CoA carboxylase