| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print February 19, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00526.2001
Submitted on November 26, 2001
Accepted on February 14, 2002
1 Department of Human Physiology, Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, Copenhagen, Denmark
2 Department of Neurology, Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark
3 Institute for Exercise and Environmental Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
4 Diabetes Research Laboratory, Winthrop University Hospital, Mineola, New York, USA
* To whom correspondence should be addressed. E-mail: jnnielsen{at}aki.ku.dk.
Insulin action is decreased by high muscle glycogen concentrations in rodent skeletal muscle. Patients with McArdle's disease have chronic high muscle glycogen levels and might therefore be at risk of developing insulin resistance. In this study, six patients with McArdles disease and 6 matched control subjects were subjected to an oral glucose tolerance test and a euglycemic hyperinsulinaemic clamp. The muscle glycogen concentration was 103 ± 45 % higher in McArdle patients than in controls. Four out of 6 McArdle patients but none of the controls had impaired glucose tolerance. The insulin-stimulated glucose utilization and the insulin-stimulated increase in glycogen synthase activity during the clamp were significantly lower in the patients than in controls (51.3 ± 6.0 versus 72.6 ± 13.1 µmol/min/kg lean body mass, p<0.05 and 53 ± 15 versus 79 ± 9 %, p<0.05, n=6, respectively). The difference in insulin-stimulated glycogen synthase activity between the pairs was significantly correlated (r=0.96, p<0.002) to the difference in muscle glycogen level. The insulin-stimulated increase in Akt phosphorylation was smaller in the McArdle patients than in controls (45 ± 13 versus 76 ± 13 %, p<0.05 respectively), whereas basal and insulin-stimulated glycogen synthase kinase 3
and protein phosphatase-1 activities were similar in the two groups. Furthermore, the ability of insulin to decrease and increase fat and carbohydrate oxidation, respectively, was blunted in the patients. In conclusion, these data show that patients with McArdle's glycogen storage disease are insulin resistant in terms of glucose uptake, glycogen synthase activation and alterations in fuel oxidation. The data further suggest that skeletal muscle glycogen levels play an important role in regulation of insulin-stimulated glycogen synthase activity.
This article has been cited by other articles:
|
|
 |
|
  J. Jensen, E. Jebens, E. O. Brennesvik, J. Ruzzin, M. A. Soos, E. M. L. Engebretsen, S. O'Rahilly, and J. P. Whitehead Muscle glycogen inharmoniously regulates glycogen synthase activity, glucose uptake, and proximal insulin signaling Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E154 - E162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lajoie, A. Calderone, F. Trudeau, N. Lavoie, G. Massicotte, S. Gagnon, and L. Beliveau Exercise training attenuated the PKB and GSK-3 dephosphorylation in the myocardium of ZDF rats J Appl Physiol, May 1, 2004; 96(5): 1606 - 1612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Vissing and R. G. Haller The Effect of Oral Sucrose on Exercise Tolerance in Patients with McArdle's Disease N. Engl. J. Med., December 25, 2003; 349(26): 2503 - 2509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. P. Wojtaszewski, J. N. Nielsen, and E. A. Richter Exercise Effects on Muscle Insulin Signaling and Action: Invited Review: Effect of acute exercise on insulin signaling and action in humans J Appl Physiol, July 1, 2002; 93(1): 384 - 392. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
