Decreased insulin action in skeletal muscle from patients with McArdle's disease

Jakob N. Nielsen, John Vissing, Jørgen F P Wojtaszewski, Ronald G. Haller, Najma Begum, Erik A. Richter

Research output: Contribution to journalArticle

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Abstract

Insulin action is decreased by high muscle glycogen concentrations in 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 McArdle's disease and six matched control subjects were subjected to an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp. The muscle glycogen concentration was 103 ± 45% higher in McArdle patients than in controls. Four of six 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 vs. 72.6 ± 13.1 μmol·min-1·kg lean body mass-1, P < 0.05, and 53 ± 15 vs. 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) with the difference in muscle glycogen level. The insulin-stimulated increase in Akt phosphorylation was smaller in the McArdle patients than in controls (45 ± 13 vs. 76 ± 13%, P < 0.05, respectively), whereas basal and insulin-stimulated glycogen synthase kinase 3α 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 the regulation of insulin-stimulated glycogen synthase activity.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume282
Issue number6 45-6
StatePublished - 2002

Fingerprint

Glycogen Storage Disease Type V
Muscle
Skeletal Muscle
Insulin
Glycogen
Glycogen Synthase
Muscles
Glucose
Clamping devices
Glycogen Storage Disease
Glycogen Synthase Kinase 3
Protein Phosphatase 1
Glucose Clamp Technique
Glucose Intolerance
Oxidation
Phosphorylation
Glucose Tolerance Test
Insulin Resistance
Fats
Carbohydrates

Keywords

  • Glucose clamp technique
  • Glycogen storage disease type V
  • Glycogen synthase
  • Glycogen synthase kinase 3
  • Protein phosphatase

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Nielsen, J. N., Vissing, J., Wojtaszewski, J. F. P., Haller, R. G., Begum, N., & Richter, E. A. (2002). Decreased insulin action in skeletal muscle from patients with McArdle's disease. American Journal of Physiology - Endocrinology and Metabolism, 282(6 45-6).

Decreased insulin action in skeletal muscle from patients with McArdle's disease. / Nielsen, Jakob N.; Vissing, John; Wojtaszewski, Jørgen F P; Haller, Ronald G.; Begum, Najma; Richter, Erik A.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 282, No. 6 45-6, 2002.

Research output: Contribution to journalArticle

Nielsen, Jakob N. ; Vissing, John ; Wojtaszewski, Jørgen F P ; Haller, Ronald G. ; Begum, Najma ; Richter, Erik A. / Decreased insulin action in skeletal muscle from patients with McArdle's disease. In: American Journal of Physiology - Endocrinology and Metabolism. 2002 ; Vol. 282, No. 6 45-6.
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