Highlights
- •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.
Abstract
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.
Abbreviations:
Aβ (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)Keywords
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Article info
Publication history
Published online: August 20, 2021
Accepted:
August 17,
2021
Received:
April 25,
2021
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