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      Effect of insulin on the brain activity obtained during visual and memory tasks in healthy human subjects.

      Neuroendocrinology
      Adolescent, Adult, Blood Glucose, analysis, Brain, drug effects, physiology, Brain Chemistry, Cognition, Evoked Potentials, Evoked Potentials, Visual, Female, Glucose Clamp Technique, Humans, Insulin, blood, Male, Memory, Neurons, Random Allocation, Reaction Time, Receptor, Insulin, Task Performance and Analysis, Vision, Ocular

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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. 2006 S. Karger AG, Basel

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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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