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Glucose transporter 3 in neuronal glucose metabolism: Health and diseases

  • Author Footnotes
    1 W. P., C. T., and L. M. contributed equally to this study.
    Wuxue Peng
    1 W. P., C. T., and L. M. contributed equally to this study.
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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  • Author Footnotes
    1 W. P., C. T., and L. M. contributed equally to this study.
    Changhong Tan
    1 W. P., C. T., and L. M. contributed equally to this study.
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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  • Author Footnotes
    1 W. P., C. T., and L. M. contributed equally to this study.
    Lijuan Mo
    1 W. P., C. T., and L. M. contributed equally to this study.
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
    Search for articles by this author
  • Jin Jiang
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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  • Wen Zhou
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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  • Juncong Du
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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  • Xuan Zhou
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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  • Xi Liu
    Corresponding authors at: 74 Linjiang Road, Yuzhong District, Chongqing 400010, China.
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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  • Lifen Chen
    Corresponding authors at: 74 Linjiang Road, Yuzhong District, Chongqing 400010, China.
    Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
    Search for articles by this author
  • Author Footnotes
    1 W. P., C. T., and L. M. contributed equally to this study.


      • GLUT3 stabilizes neuronal glucose uptake and utilization, influences brain development and function and ameliorates aging.
      • GLUT3 is regulated by synaptic activity, hormones, nutrition, insulin, IGF1, and hypoxia-ischemia.
      • GLUT3 participates in various diseases of nervous system, and influence their progression and prognosis.


      Neurons obtain glucose from extracellular environment for energy production mainly depending on glucose transporter 3 (GLUT3). GLUT3 uptakes glucose with high affinity and great transport capacity, and is important for neuronal energy metabolism. This review summarized the role of neuronal GLUT3 in brain metabolism, function and development under both physiological conditions and in diseases, aiming to provide insights into neuronal glucose metabolism and its effect on brain. GLUT3 stabilizes neuronal glucose uptake and utilization, influences brain development and function, and ameliorates aging-related manifestations. Neuronal GLUT3 is regulated by synaptic activity, hormones, nutrition, insulin and insulin-like growth factor 1 in physiological conditions, and is also upregulated by hypoxia-ischemia. GLUT3-related neuronal glucose and energy metabolism is possibly involved in the pathogenesis, pathophysiological mechanism, progression or prognosis of brain diseases, including Alzheimer's disease, Huntington's disease, attention-deficit/hyperactivity disorder and epilepsy. GLUT3 may be a promising therapeutic target of these diseases. This review also briefly discussed the role of other glucose transporters in neuronal glucose metabolism, which work together with GLUT3 to sustain and stabilize glucose and energy supply for neurons. Deficiency in these glucose transporters may also participate in brain diseases, especially GLUT1 and GLUT4.


      (amyloid beta), AD (Alzheimer's disease), ADHD (attention-deficit/hyperactivity disorder), AMPK (adenosine 5′-monophosphate-activated protein kinase), BBB (blood-brain barrier), cAMP (cyclic adenosine monophosphate), cGK (cGMP-dependent protein kinase), CNS (center nerve system), CREB (cAMP-response element binding protein), CSF (cerebrospinal fluid), GC (guanylate cyclase), GLUTs (glucose transporter proteins), HD (Huntington's disease), HIF-1α (hypoxia-inducible factor-1α), IGF1 (insulin-like growth factor 1), lCMRglc (local cerebral metabolic rate of glucose), mTOR (mammalian target of rapamycin), NMDAR (N-methyl-D-aspartic acid receptor), nNOS (nitric oxide synthase), NO (nitric oxide), PKA (protein kinase A), PI3K (phosphatidylinositol 3-kinase), TM (transmembrane domain)


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