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      Effect of Insulin on the Brain Activity Obtained during Visual and Memory Tasks in Healthy Human Subjects

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          Abstract

          Insulin receptors are found throughout the brain, particularly in the hippocampus, although the impact of insulin on memory is unclear. The purpose of this study was to examine the effect of insulin on event-related potentials in response to a standard memory task and visual evoked potentials (VEPs) during exposure to a reversing checkerboard. We hypothesized that insulin would decrease P300 magnitude and latency during the presentation of previously observed stimuli, but would have no effect on VEPs. Sixteen humans participated in two euglycemic clamp studies with somatostatin performed in random order in which serum insulin levels were either suppressed (14 ± 1 pmol/l) or increased by insulin infusion (433 ± 40 pmol/l). At steady state, event-related potentials and then VEPs were collected using a 32-electrode cap. The major finding was that the P300 amplitude measured during the identification of an object as old was significantly smaller over parietal regions when insulin was infused than when no insulin was provided. Insulin was without effect on the VEPs. We conclude that insulin has region- and task-specific effects on neuronal activation. While the P300 amplitude measured during the presentation of an old object was reduced during insulin infusion, the hormone was without effect on VEPs.

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          Most cited references18

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          The role of insulin receptor signaling in the brain.

          The insulin receptor (IR) is expressed in various regions of the developing and adult brain, and its functions have become the focus of recent research. Insulin enters the central nervous system (CNS) through the blood-brain barrier by receptor-mediated transport to regulate food intake, sympathetic activity and peripheral insulin action through the inhibition of hepatic gluconeogenesis and reproductive endocrinology. On a molecular level, some of the effects of insulin converge with those of the leptin signaling machinery at the point of activation of phosphatidylinositol 3-kinase (PI3K), resulting in the regulation of ATP-dependent potassium channels. Furthermore, insulin inhibits neuronal apoptosis via activation of protein kinase B in vitro, and it regulates phosphorylation of tau, metabolism of the amyloid precursor protein and clearance of beta-amyloid from the brain in vivo. These findings indicate that neuronal IR signaling has a direct role in the link between energy homeostasis, reproduction and the development of neurodegenerative diseases.
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              Localization of insulin receptor mRNA in rat brain by in situ hybridization.

              Insulin receptor mRNA was demonstrated in rat brain slices by in situ hybridization with three 35S-oligonucleotide probes and contact film autoradiography. Specificity was confirmed by showing that (a) excess unlabeled probe abolished the signal, (b) an oligonucleotide probe for rat neuropeptide Y mRNA showed a different distribution of hybridization signal, and (c) the distribution of insulin receptor binding was consistent with the distribution of insulin receptor mRNA. Insulin receptor mRNA was most abundant in the granule cell layers of the olfactory bulb, cerebellum and dentate gyrus, in the pyramidal cell body layers of the pyriform cortex and hippocampus, in the choroid plexus and in the arcuate nucleus of the hypothalamus.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2006
                June 2006
                13 June 2006
                : 83
                : 1
                : 20-26
                Affiliations
                aDepartment of Medicine, School of Medicine, bDepartment of Psychology, University of Minnesota, Minneapolis, Minn., and cHarvard Medical School, Children’s Hospital, Boston, Mass., USA
                Article
                93338 Neuroendocrinology 2006;83:20–26
                10.1159/000093338
                16707912
                2ac6ba61-8f88-4bad-a164-960ea2e9883e
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 12 January 2006
                : 06 April 2006
                Page count
                Figures: 2, Tables: 6, References: 26, Pages: 7
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Insulin,Evoked response potentials,Neuronal activation,Memory,Cognition

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