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The Journal of Neuroscience, April 22, 2009, 29(16):5193-5201; doi:10.1523/JNEUROSCI.0858-09.2009

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Cellular/Molecular
Cerebellar Neurons Possess a Vesicular Compartment Structurally and Functionally Similar to Glut4-Storage Vesicles from Peripheral Insulin-Sensitive Tissues

Kyriaki Bakirtzi,1 Gabriel Belfort,1 Ignacio Lopez-Coviella,2 Darshini Kuruppu,3 Lei Cao,3 E. Dale Abel,4 Anna-Liisa Brownell,3 and Konstantin V. Kandror1

Departments of 1Biochemistry and 2Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118, 3Massachusetts General Hospital, Boston, Massachusetts 02114, and 4Division of Endocrinology, Metabolism, and Diabetes and the Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84112

Correspondence should be addressed to Konstantin V. Kandror, Boston University School of Medicine, Department of Biochemistry, K124D, 715 Albany Street, Boston, MA 02118. Email: kandror{at}biochem.bumc.bu.edu

The insulin-sensitive isoform of the glucose transporting protein, Glut4, is expressed in fat as well as in skeletal and cardiac muscle and is responsible for the effect of insulin on blood glucose clearance. Recent studies have revealed that Glut4 is also expressed in the brain, although the intracellular compartmentalization and regulation of Glut4 in neurons remains unknown. Using sucrose gradient centrifugation, immunoadsorption and immunofluorescence staining, we have shown that Glut4 in the cerebellum is localized in intracellular vesicles that have the sedimentation coefficient, the buoyant density, and the protein composition similar to the insulin-responsive Glut4-storage vesicles from fat and skeletal muscle cells. In cultured cerebellar neurons, insulin stimulates glucose uptake and causes translocation of Glut4 to the cell surface. Using 18FDG (18fluoro-2-deoxyglucose) positron emission tomography, we found that physical exercise acutely increases glucose uptake in the cerebellum in vivo. Prolonged physical exercise increases expression of the Glut4 protein in the cerebellum. Our results suggest that neurons have a novel type of translocation-competent vesicular compartment which is regulated by insulin and physical exercise similar to Glut4-storage vesicles in peripheral insulin target tissues.

Received Feb. 19, 2009; accepted March 11, 2009.

Correspondence should be addressed to Konstantin V. Kandror, Boston University School of Medicine, Department of Biochemistry, K124D, 715 Albany Street, Boston, MA 02118. Email: kandror{at}biochem.bumc.bu.edu






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