title: Cardiac glycogen accumulation after dexamethasone is regulated by AMPK.
abstract: 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 5'-AMP-activated protein kinase (AMPK) on glucose entry and glycogen synthase as a means of regulating the accumulation of this stored polysaccharide. After Dex, cardiac tissue had a limited contribution toward the development of whole body insulin resistance. Measurement of glucose transporter 4 (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 with increased GLUT4 mRNA. Both total and phosphorylated AMPK increased after Dex. Immunoprecipitation of Akt substrate of 160 kDa (AS160) followed by Western blot analysis demonstrated no change in Akt phosphorylation at Ser(473) and Thr(308) in Dex-treated hearts. However, there was a significant increase in AMPK phosphorylation at Thr(172), which correlated well with AS160 phosphorylation. In Dex-treated hearts, there was a considerable reduction in the phosphorylation of glycogen synthase, whereas glycogen synthase kinase-3-beta phosphorylation was augmented. Our data suggest that AMPK-mediated glucose entry combined with the activation of glycogen synthase and a reduction in glucose oxidation (Qi et al., Diabetes 53: 1790-1797, 2004) act together to promote glycogen storage. Should these effects persist chronically in the heart, they may explain the increased morbidity and mortality observed with long-term excesses in endogenous or exogenous glucocorticoids.
authors.affiliation: Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Prasanth
authors.initials: P
authors.lastname: Puthanveetil
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Girish
authors.initials: G
authors.lastname: Kewalramani
authors.forename: Min Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Elham
authors.initials: E
authors.lastname: Hosseini-Beheshti
authors.forename: Natalie
authors.initials: N
authors.lastname: Ng
authors.forename: William
authors.initials: W
authors.lastname: Lau
authors.forename: Thomas
authors.initials: T
authors.lastname: Pulinilkunnil
authors.forename: Michael
authors.initials: M
authors.lastname: Allard
authors.forename: Ashraf
authors.initials: A
authors.lastname: Abrahani
authors.forename: Brian
authors.initials: B
authors.lastname: Rodrigues