| Cardiac glycogen accumulation after dexamethasone is regulated by AMPK. | |
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MedLine Citation:
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PMID: 18757479 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Prasanth Puthanveetil; Fang Wang; Girish Kewalramani; Min Suk Kim; Elham Hosseini-Beheshti; Natalie Ng; William Lau; Thomas Pulinilkunnil; Michael Allard; Ashraf Abrahani; Brian Rodrigues |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-29 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 295 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-08 Completed Date: 2008-12-05 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1753-62 Citation Subset: IM |
Affiliation:
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Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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metabolism* Animals Carbohydrate Metabolism / drug effects Dexamethasone / pharmacology* Glucose Transporter Type 4 / genetics, metabolism Glycogen / metabolism* Glycogen Synthase Kinase 3 / metabolism Insulin Resistance Male Myocardium / enzymology* Phosphorylation Protein Transport Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / metabolism Rats Rats, Wistar Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Glucose Transporter Type 4; 0/RNA, Messenger; 0/Slc2a4 protein, rat; 50-02-2/Dexamethasone; 9005-79-2/Glycogen; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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