Peripheral glucose administration stimulates the translocation of GLUT8 glucose transporter to the endoplasmic reticulum in the rat hippocampus

Gerardo G. Piroli, Claudia A. Grillo, Elena K. Hoskin, Vladimir Znamensky, Ellen B. Katz, Teresa A. Milner, Bruce S. McEwen, Maureen J. Charron, Lawrence P. Reagan

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The expression and localization of glucose transporter isoforms play essential roles in the glucoregulatory activities of the hippocampus and ultimately contribute to cognitive status in physiological and pathophysiological settings. The recently identified glucose transporter GLUT8 is uniquely expressed in neuronal cell bodies in the rat hippocampus and therefore may contribute to hippocampal glucoregulatory activities. We show here that GLUT8 has a novel intracellular distribution in hippocampal neurons and is translocated to intracellular membranes following glucose challenge. Immunoblot analysis revealed that GLUT8 is expressed in high-density microsomes (HDM), suggesting that GLUT8 is associated with intracellular organelles under basal conditions. Immunogold electron microscopic analysis confirmed this observation, in that GLUT8 immunogold particles were associated with the rough endoplasmic reticulum (ER) and cytoplasm. Peripheral glucose administration produced a rapid twofold increase in GLUT8 levels in the HDM fraction while decreasing GLUT8 levels in low-density microsomes. Similarly, peripheral glucose administration significantly increased GLUT8 association with the rough ER in the hippocampus. Conversely, under hyperglycemic/insulinopenic conditions, namely, in streptozotocin (STZ) diabetes, hippocampal GLUT8 protein levels were decreased in the HDM fraction. These results demonstrate that GLUT8 undergoes rapid translocation to the rough ER in the rat hippocampus following peripheral glucose administration, trafficking that is impaired in STZ diabetes, suggesting that insulin serves as a stimulus for GLUT8 translocation in hippocampal neurons. Because glucose is liberated from oligosaccharides during N-linked glycosylation events in the rough ER, we propose that GLUT8 may serve to transport glucose out of the rough ER into the cytosol and in this manner contribute to glucose homeostasis in hippocampal neurons.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalJournal of Comparative Neurology
Volume452
Issue number2
DOIs
StatePublished - Oct 14 2002

Fingerprint

Facilitative Glucose Transport Proteins
Endoplasmic Reticulum
Hippocampus
Rough Endoplasmic Reticulum
Glucose
Microsomes
Experimental Diabetes Mellitus
Neurons
Intracellular Membranes
Oligosaccharides
Glycosylation
Organelles
Cytosol
Protein Isoforms
Cytoplasm
Homeostasis
Electrons
Insulin

Keywords

  • Cognition
  • Diabetes
  • GLUTx1
  • Insulin
  • N-linked glycosylation
  • Streptozotocin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Peripheral glucose administration stimulates the translocation of GLUT8 glucose transporter to the endoplasmic reticulum in the rat hippocampus. / Piroli, Gerardo G.; Grillo, Claudia A.; Hoskin, Elena K.; Znamensky, Vladimir; Katz, Ellen B.; Milner, Teresa A.; McEwen, Bruce S.; Charron, Maureen J.; Reagan, Lawrence P.

In: Journal of Comparative Neurology, Vol. 452, No. 2, 14.10.2002, p. 103-114.

Research output: Contribution to journalArticle

Piroli, Gerardo G. ; Grillo, Claudia A. ; Hoskin, Elena K. ; Znamensky, Vladimir ; Katz, Ellen B. ; Milner, Teresa A. ; McEwen, Bruce S. ; Charron, Maureen J. ; Reagan, Lawrence P. / Peripheral glucose administration stimulates the translocation of GLUT8 glucose transporter to the endoplasmic reticulum in the rat hippocampus. In: Journal of Comparative Neurology. 2002 ; Vol. 452, No. 2. pp. 103-114.
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AU - Znamensky, Vladimir

AU - Katz, Ellen B.

AU - Milner, Teresa A.

AU - McEwen, Bruce S.

AU - Charron, Maureen J.

AU - Reagan, Lawrence P.

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AB - The expression and localization of glucose transporter isoforms play essential roles in the glucoregulatory activities of the hippocampus and ultimately contribute to cognitive status in physiological and pathophysiological settings. The recently identified glucose transporter GLUT8 is uniquely expressed in neuronal cell bodies in the rat hippocampus and therefore may contribute to hippocampal glucoregulatory activities. We show here that GLUT8 has a novel intracellular distribution in hippocampal neurons and is translocated to intracellular membranes following glucose challenge. Immunoblot analysis revealed that GLUT8 is expressed in high-density microsomes (HDM), suggesting that GLUT8 is associated with intracellular organelles under basal conditions. Immunogold electron microscopic analysis confirmed this observation, in that GLUT8 immunogold particles were associated with the rough endoplasmic reticulum (ER) and cytoplasm. Peripheral glucose administration produced a rapid twofold increase in GLUT8 levels in the HDM fraction while decreasing GLUT8 levels in low-density microsomes. Similarly, peripheral glucose administration significantly increased GLUT8 association with the rough ER in the hippocampus. Conversely, under hyperglycemic/insulinopenic conditions, namely, in streptozotocin (STZ) diabetes, hippocampal GLUT8 protein levels were decreased in the HDM fraction. These results demonstrate that GLUT8 undergoes rapid translocation to the rough ER in the rat hippocampus following peripheral glucose administration, trafficking that is impaired in STZ diabetes, suggesting that insulin serves as a stimulus for GLUT8 translocation in hippocampal neurons. Because glucose is liberated from oligosaccharides during N-linked glycosylation events in the rough ER, we propose that GLUT8 may serve to transport glucose out of the rough ER into the cytosol and in this manner contribute to glucose homeostasis in hippocampal neurons.

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