Glycogen is an immediate source of glucose for cardiac tissue to maintain its metabolic
homeostasis. However, its excess brings about cardiac structural and physiological
impairments. Previously, we have demonstrated that in hearts from dexamethasone
(DEX) treated animals, glycogen accumulation was enhanced. We examined the
influence of DEX on glucose entry and glycogen synthase as a means of regulating the
accumulation of this stored polysaccharide. Following DEX, cardiac tissue had limited
contribution towards the development of whole body insulin resistance. Measurement of
GLUT4 at the plasma membrane revealed an excess presence of this transporter protein
at this location. Interestingly, this was accompanied by an increase in GLUT4 in the
intracellular membrane fraction, an effect that was well correlated to an increased
GLUT4 mR.NA. Both total and phosphorylated AMPK increased following DEX.
Immunoprecipitation of AS 160 followed by Western blotting demonstrated no change in
Akt phosphorylation at Ser473 and Thr308 in DEX treated hearts. However, there was a
significant increase in AMPK phosphorylation at Thr172, which correlated well with
AS 160 phosphorylation. In DEX hearts, there was a considerable reduction in the
phosphorylation of glycogen synthase, whereas GSK-3-β phosphorylation was
augmented. Our data suggest that AMPK mediated glucose entry, combined with
activation of glycogen synthase and reduction in glucose oxidation (Qi, D., et al. Diabetes
53:1790, 2004), act together to promote glycogen storage. Our data suggest that in the
presence of intact insulin signaling, AMPK mediated glucose entry, combined with
activation of glycogen synthase and the previously reported reduction in glucose
oxidation, act together to promote glycogen storage. Should these effects persist chronically, they may explain the increased morbidity and mortality observed with long
term excesses in endogenous or exogenous glucocorticoids.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU./5038 |
| Date | 11 1900 |
| Creators | Puthanveetil, Prasanth Nair |
| Publisher | University of British Columbia |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | 1393576 bytes, application/pdf |
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