title: Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependent.
abstract: In the central nervous system (CNS) insulin mediates a variety of effects including feeding, metabolism and cognition. The cognitive enhancing effects of insulin are proposed to be mediated through activation of insulin receptors in the hippocampus, an important integration center for learning and memory in the mammalian brain. Since less is known regarding insulin signaling events in the hippocampus, the aim of the current study was to determine whether insulin stimulates similar signaling cascades and GLUT4 translocation in the rat hippocampus as has been described in peripheral tissues. Intracerebroventricular administration of insulin increases hippocampal insulin levels and also stimulates the phosphorylation of Akt in a time-dependent manner. Insulin also stimulates the translocation of GLUT4 to hippocampal plasma membranes in a time course that mirrors the increases in glucose uptake observed during the performance of hippocampal-dependent tasks. Insulin stimulated phosphorylation of Akt and translocation of GLUT4 were blocked by pretreatment with the PI3-kinase inhibitor LY294002. Confocal immunofluorescence determined that insulin stimulated phosphorylation of Akt was localized to neurons and colocalized with the insulin receptor and GLUT4 in the rat hippocampus, thereby identifying the functional anatomical substrates of insulin signaling in the hippocampus. These results demonstrate that insulin-stimulated translocation of GLUT4 to the plasma membrane in the rat hippocampus occurs via similar mechanisms as described in peripheral tissues and suggests that insulin-mediated translocation of GLUT4 may provide a mechanism through which hippocampal neurons rapidly increase glucose utilization during increases in neuronal activity associated with hippocampal-dependent learning.
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garner's Ferry Road, Columbia, SC 29208, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Grillo
authors.forename: G G
authors.initials: GG
authors.lastname: Piroli
authors.forename: R M
authors.initials: RM
authors.lastname: Hendry
authors.forename: L P
authors.initials: LP
authors.lastname: Reagan
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D013997:Time Factors
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D007328:Insulin; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; C495694:Slc2a4 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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