The insulin receptor (IR) is a protein tyrosine kinase playing a pivotal role in the regulation of peripheral glucose metabolism and energy homoeostasis. IRs are also abundantly distributed in the cerebral cortex and hippocampus, where they regulate synaptic activity required for learning and memory. As the major anabolic hormone in mammals, insulin stimulates protein synthesis partially through the activation of the PI3K/Akt/mTOR pathway, playing fundamental roles in neuronal development, synaptic plasticity and memory. Here, by means of a multidisciplinary approach, we report that long-term synaptic plasticity and recognition memory are impaired in IR β-subunit heterozygous mice. Since IR expression is diminished in type-2 diabetes as well as in Alzheimer's disease (AD) patients, these data may provide a mechanistic link between insulin resistance, impaired synaptic transmission and cognitive decline in humans with metabolic disorders.

Nistico', R.g., Cavallucci, V., Piccinin, S., Macrì, S., Pignatelli, M., Mehdawy, B., et al. (2012). Insulin receptor β-subunit haploinsufficiency impairs hippocampal late-phase LTP and recognition memory. NEUROMOLECULAR MEDICINE, 14(4), 262-269 [10.1007/s12017-012-8184-z].

Insulin receptor β-subunit haploinsufficiency impairs hippocampal late-phase LTP and recognition memory

NISTICO', ROBERT GIOVANNI;LAURO, DAVIDE;MERCURI, NICOLA BIAGIO;
2012-12-01

Abstract

The insulin receptor (IR) is a protein tyrosine kinase playing a pivotal role in the regulation of peripheral glucose metabolism and energy homoeostasis. IRs are also abundantly distributed in the cerebral cortex and hippocampus, where they regulate synaptic activity required for learning and memory. As the major anabolic hormone in mammals, insulin stimulates protein synthesis partially through the activation of the PI3K/Akt/mTOR pathway, playing fundamental roles in neuronal development, synaptic plasticity and memory. Here, by means of a multidisciplinary approach, we report that long-term synaptic plasticity and recognition memory are impaired in IR β-subunit heterozygous mice. Since IR expression is diminished in type-2 diabetes as well as in Alzheimer's disease (AD) patients, these data may provide a mechanistic link between insulin resistance, impaired synaptic transmission and cognitive decline in humans with metabolic disorders.
dic-2012
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/13 - ENDOCRINOLOGIA
English
Con Impact Factor ISI
post-synaptic density; animals; TOR serine-threonine kinases; hippocampus; humans; Alzheimer disease; proto-oncogene proteins c-akt; mice; learning disorders; memory disorders; phosphatidylinositol 3-kinases; nerve tissue proteins; recognition (psychology); heterozygote; diabetes mellitus, type 2; insulin resistance; receptor, insulin; long-term potentiation; synaptic transmission; signal transduction; female
Nistico', R.g., Cavallucci, V., Piccinin, S., Macrì, S., Pignatelli, M., Mehdawy, B., et al. (2012). Insulin receptor β-subunit haploinsufficiency impairs hippocampal late-phase LTP and recognition memory. NEUROMOLECULAR MEDICINE, 14(4), 262-269 [10.1007/s12017-012-8184-z].
Nistico', Rg; Cavallucci, V; Piccinin, S; Macrì, S; Pignatelli, M; Mehdawy, B; Blandini, F; Laviola, G; Lauro, D; Mercuri, Nb; D'Amelio, M...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/78093
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