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Robert A. Harris  (Harris RA) 1 Article
Role of Pyruvate Dehydrogenase Kinase 4 in Regulation of Blood Glucose Levels
Nam Ho Jeoung, Robert A. Harris
Korean Diabetes J. 2010;34(5):274-283.   Published online October 31, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.5.274
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AbstractAbstract PDFPubReader   

In the well-fed state a relatively high activity of the pyruvate dehydrogenase complex (PDC) reduces blood glucose levels by directing the carbon of pyruvate into the citric acid cycle. In the fasted state a relatively low activity of the PDC helps maintain blood glucose levels by conserving pyruvate and other three carbon compounds for gluconeogenesis. The relative activities of the pyruvate dehydrogenase kinases (PDKs) and the opposing pyruvate dehydrogenase phosphatases determine the activity of PDC in the fed and fasted states. Up regulation of PDK4 is largely responsible for inactivation of PDC in the fasted state. PDK4 knockout mice have lower fasting blood glucose levels than wild type mice, proving that up regulation of PDK4 is important for normal glucose homeostasis. In type 2 diabetes, up regulation of PDK4 also inactivates PDC, which promotes gluconeogenesis and thereby contributes to the hyperglycemia characteristic of this disease. When fed a high fat diet, wild type mice develop fasting hyperglycemia but PDK4 knockout mice remain euglycemic, proving that up regulation of PDK4 contributes to hyperglycemia in diabetes. These finding suggest PDK4 inhibitors might prove useful in the treatment of type 2 diabetes.

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    Experimental & Molecular Medicine.2021; 53(9): 1390.     CrossRef
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    BMB Reports.2021; 54(11): 563.     CrossRef
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    Khalia R. Primer, Peter J. Psaltis, Joanne T.M. Tan, Christina A. Bursill
    International Journal of Molecular Sciences.2020; 21(10): 3633.     CrossRef
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    Fengqiong Liu, Qing Chen, Fa Chen, Jing Wang, Ruijie Gong, Baochang He
    Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids.2019; 1864(10): 1449.     CrossRef
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    Wu, Gunton
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    Don-Kyu Kim, Hueng-Sik Choi
    Liver Research.2019; 3(2): 99.     CrossRef
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    Xenobiotica.2019; 49(5): 577.     CrossRef
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    Rafael L. Rosa, Markus Berger, Lucélia Santi, David Driemeier, Paula Barros Terraciano, Alexandre R. Campos, Jorge A. Guimarães, Marilene H. Vainstein, John R. Yates, Walter O. Beys-da-Silva
    Journal of Proteome Research.2019; 18(11): 3885.     CrossRef
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    Experimental Brain Research.2018; 236(11): 2857.     CrossRef
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    Jayant Lohakare, Johan S Osorio, Massimo Bionaz
    Journal of Dairy Research.2018; 85(3): 295.     CrossRef
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    Biomedicine & Pharmacotherapy.2017; 85: 725.     CrossRef
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    Chemico-Biological Interactions.2016; 250: 38.     CrossRef
  • Inflammation increases pyruvate dehydrogenase kinase 4 (PDK4) expression via the Jun N-Terminal Kinase (JNK) pathway in C2C12 cells
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    Biochemical and Biophysical Research Communications.2016; 469(4): 1049.     CrossRef
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    Pharmacogenomics.2011; 12(7): 985.     CrossRef

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