Exercise training does not correct abnormal cardiac glycogen accumulation in the db/db mouse model of type 2 diabetes

Jane Shearer, Karen D. Ross, Curtis C. Hughey, Virginia L. Johnsen, Dustin S. Hittel, David L. Severson

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29 Scopus citations


Substrate imbalance is a well-recognized feature of diabetic cardiomyopathy. Insulin resistance effectively limits carbohydrate oxidation, resulting in abnormal cardiac glycogen accumulation. Aims of the present study were to 1) characterize the role of glycogen-associated proteins involved in excessive glycogen accumulation in type 2 diabetic hearts and 2) determine if exercise training can attenuate abnormal cardiac glycogen accumulation. Control (db+) and genetically diabetic (db/ db) C57BL/KsJ-leprdb/leprdb mice were subjected to sedentary or treadmill exercise regimens. Exercise training consisted of highintensity/ short-duration (10 days) and low-intensity/long-duration (6 wk) protocols. Glycogen levels were elevated by 35-50% in db/db hearts. Exercise training further increased (2- to 3-fold) glycogen levels in db/db hearts. Analysis of soluble and insoluble glycogen pools revealed no differential accumulation of one glycogen subspecies. Phosphorylation (Ser640) of glycogen synthase, an indicator of enzymatic fractional activity, was greater in db/db mice subjected to sedentary and exercise regimens. Elevated glycogen levels were accompanied by decreased phosphorylation (Thr172) of 5′-AMPactivated kinase and phosphorylation (Ser79) of its downstream substrate acetyl-CoA carboxylase. Glycogen concentration was not associated with increases in other glycogen-associated proteins, including malin and laforin. Novel observations show that exercise training does not correct diabetes-induced elevations in cardiac glycogen but, rather, precipitates further accumulation.

Original languageEnglish (US)
Pages (from-to)E31-E39
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1
StatePublished - Jul 2011
Externally publishedYes


  • Metabolism
  • Proglycogen


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