期刊
NEUROMOLECULAR MEDICINE
卷 14, 期 4, 页码 262-269出版社
HUMANA PRESS INC
DOI: 10.1007/s12017-012-8184-z
关键词
Diabetes; Insulin receptor signalling; Long-term potentiation; Synaptic plasticity; Cognitive decline
资金
- Italian Ministry of Health
- Alzheimer's Association [NIRG-11-204588]
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 beta-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.
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