Glucose metabolism in mice lacking muscle glycogen synthase

Bartholomew A. Pederson, Jill M. Schroeder, Gretchen E. Parker, Micah W. Smith, Anna De Paoli-Roach, Peter Roach

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Glycogen is an important component of whole-body glucose metabolism. MGSKO mice lack skeletal muscle glycogen due to disruption of the GYS1 gene, which encodes muscle glycogen synthase. MGSKO mice were 5-10% smaller than wild-type littermates with less body fat. They have more oxidative muscle fibers and, based on the activation state of AMP-activated protein kinase, more capacity to oxidize fatty acids. Blood glucose in fed and fasted MGSKO mice was comparable to wild-type littermates. Serum insulin was lower in fed but not in fasted MGSKO animals. In a glucose tolerance test, MGSKO mice disposed of glucose more effectively than wild-type animals and had a more sustained elevation of serum insulin. This result was not explained by increased conversion to serum lactate or by enhanced storage of glucose in the liver. However, glucose infusion rate in a euglycemic-hyperinsulinemic clamp was normal in MGSKO mice despite diminished muscle glucose uptake. During the clamp, MGSKO animals accumulated significantly higher levels of liver glycogen as compared with wild-type littermates. Although disruption of the GYS1 gene negatively affects muscle glucose uptake, overall glucose tolerance is actually improved, possibly because of a role for GYS1 in tissues other than muscle.

Original languageEnglish
Pages (from-to)3466-3473
Number of pages8
JournalDiabetes
Volume54
Issue number12
DOIs
StatePublished - Dec 2005

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Glycogen Synthase
Glucose
Muscles
Glycogen
Serum
Insulin
Liver Glycogen
AMP-Activated Protein Kinases
Glucose Clamp Technique
Wild Animals
Glucose Tolerance Test
Genes
Blood Glucose
Adipose Tissue
Lactic Acid
Skeletal Muscle
Fatty Acids
Liver

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucose metabolism in mice lacking muscle glycogen synthase. / Pederson, Bartholomew A.; Schroeder, Jill M.; Parker, Gretchen E.; Smith, Micah W.; De Paoli-Roach, Anna; Roach, Peter.

In: Diabetes, Vol. 54, No. 12, 12.2005, p. 3466-3473.

Research output: Contribution to journalArticle

Pederson, BA, Schroeder, JM, Parker, GE, Smith, MW, De Paoli-Roach, A & Roach, P 2005, 'Glucose metabolism in mice lacking muscle glycogen synthase', Diabetes, vol. 54, no. 12, pp. 3466-3473. https://doi.org/10.2337/diabetes.54.12.3466
Pederson, Bartholomew A. ; Schroeder, Jill M. ; Parker, Gretchen E. ; Smith, Micah W. ; De Paoli-Roach, Anna ; Roach, Peter. / Glucose metabolism in mice lacking muscle glycogen synthase. In: Diabetes. 2005 ; Vol. 54, No. 12. pp. 3466-3473.
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