Insulin and the brain.
Insulin and the brain.
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DOI：
10.2174/1573399811309020002
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发表时间：
2013-02
影响因子：
3.3
通讯作者：
F. Derakhshan;C. Toth
中科院分区：
文献类型：
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作者：
F. Derakhshan;C. Toth
胰岛素主要以其在外周葡萄糖稳态中的作用而闻名，在大脑中也有显著的影响，在行为、细胞、生物化学和分子研究中作为关键的神经调节剂发挥作用。脑现在被认为是胰岛素敏感的器官，在嗅球、下丘脑、海马、小脑、杏仁核和大脑皮层中广泛但选择性地表达胰岛素受体。脑中的胰岛素受体信号传导对于神经元发育、葡萄糖调节、进食行为、体重和认知过程（例如注意力、执行功能、学习和记忆）是重要的。新出现的证据表明，胰岛素受体信号传导在几种神经系统疾病中受损。此外，胰岛素受体信号传导被认为对树突生长、神经元存活、回路发育、突触可塑性和突触后神经递质受体运输是重要的。我们回顾了胰岛素在大脑中的多种作用，以及其内源性运输到大脑或其外源性干预。虽然胰岛素可以通过脑室内（ICV）或脑实质内递送直接靶向大脑，但这些侵入性技术具有显著风险，需要反复手术干预并可能导致全身性低血糖。另一种方法，鼻内递送，是一种非侵入性的、安全的和替代的方法，其将分子快速靶向递送至大脑，同时使全身暴露最小化。在过去的几十年里，在动物模型和人类患者中鼻内胰岛素的递送已经发展和扩展，为相关的神经退行性和神经血管疾病带来了新的希望。
Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting new hope for associated neurodegenerative and neurovascular disorders.