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

Kyriaki Bakirtzi; Gabriel Belfort; Ignacio Lopez-Coviella; Darshini Kuruppu; Lei Cao; E. Dale Abel; Anna-Liisa Brownell; Konstantin V Kandror

doi:10.1523/JNEUROSCI.0858-09.2009

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

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

Kyriaki Bakirtzi, Gabriel Belfort, Ignacio Lopez-Coviella, Darshini Kuruppu, Lei Cao, E. Dale Abel, Anna-Liisa Brownell and Konstantin V Kandror

The Journal of neuroscience, Vol.29(16), pp.5193-5201

04/22/2009

DOI: 10.1523/JNEUROSCI.0858-09.2009

PMCID: PMC2692175

PMID: 19386915

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Abstract

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 18 FDG ( 18 fluoro-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.

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Title: Subtitle: Cerebellar Neurons Possess a Vesicular Compartment Structurally and Functionally Similar to Glut4-Storage Vesicles from Peripheral Insulin-Sensitive Tissues
Creators: Kyriaki Bakirtzi - Departments of
Gabriel Belfort - Departments of
Ignacio Lopez-Coviella - Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118
Darshini Kuruppu - Massachusetts General Hospital, Boston, Massachusetts 02114, and
Lei Cao - Massachusetts General Hospital, Boston, Massachusetts 02114, and
E. Dale Abel - Division of Endocrinology, Metabolism, and Diabetes and the Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah 84112
Anna-Liisa Brownell - Massachusetts General Hospital, Boston, Massachusetts 02114, and
Konstantin V Kandror - Departments of
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.29(16), pp.5193-5201
Publisher: Society for Neuroscience
DOI: 10.1523/JNEUROSCI.0858-09.2009
PMID: 19386915
PMCID: PMC2692175
ISSN: 0270-6474
eISSN: 1529-2401
Language: English
Date published: 04/22/2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024524202771

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