<br>下丘脑神经元中的胰岛素信号传导,Journal of Neuroendocrinology

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下丘脑神经元中的胰岛素信号传导
Journal of Neuroendocrinology ( IF 3.3 ) Pub Date : 2020-11-07 , DOI: 10.1111/jne.12919
Denise D Belsham ₁ , Prasad S Dalvi ₂

Affiliation

100 年前，多伦多大学生理学系的班廷 (Banting) 和贝斯特 (Best) 发现了胰岛素，此后，胰岛素信号传导和作用领域以惊人的速度发展。然而，直到最近才认识到大脑中的胰岛素作用对于全身稳态至关重要。下丘脑是大脑中的一个关键区域，它通过复杂的信号级联反应对循环胰岛素做出反应，最终释放控制饥饿和进食的神经肽。这一重要反馈系统的破坏可能会导致一种称为细胞胰岛素抵抗的现象，即神经元不再感知胰岛素。导致胰岛素抵抗的因素以及由此产生的有害影响包括诱导神经炎症、内质网应激以及允许胰岛素转运至大脑的血脑屏障结构的改变。这些表现通常会改变能量平衡，导致体重增加，常常导致肥胖及其致命的合并症，包括 2 型糖尿病、心血管疾病和代谢综合征。尽管如此，仍然存在希望，因为信号转导途径可以通过神经元特异性治疗在多个水平上进行靶向。随着用于研究这些过程所涉及机制的独特细胞模型的出现，发现新靶标的可能性越来越大。尽管我们仍在寻找治疗糖尿病的方法，但班廷和贝斯特会对他们的发现取得的进展以及基于胰岛素作用积累的当代知识印象深刻。

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Insulin signalling in hypothalamic neurones

Subsequent to the discovery of insulin by Banting and Best in the Department of Physiology at the University of Toronto 100 years ago, the field of insulin signalling and action has grown at a remarkable pace. Yet, the recognition that insulin action in the brain is critical for whole body homeostasis has only recently been appreciated. The hypothalamus is a key region in the brain that responds to circulating insulin by engaging a complex signalling cascade resulting in the ultimate release of neuropeptides that control hunger and feeding. Disruption of this important feedback system can lead to a phenomenon called cellular insulin resistance, where the neurones cease to sense insulin. The factors contributing to insulin resistance, as well as the resulting detrimental effects, include the induction of neuroinflammation, endoplasmic reticulum stress and alterations in the architecture of the blood‐brain barrier that allow transport of insulin into the brain. These manifestations usually change energy balance, causing weight gain, often resulting in obesity and its deadly comorbidities, including type 2 diabetes mellitus, cardiovascular disease and metabolic syndrome. Nonetheless, there is still hope because the signal transduction pathways can be targeted at a number of levels by neurone‐specific therapeutics. With the advent of unique cell models for investigating the mechanisms involved in these processes, the discovery of novel targets is increasingly possible. Although we are still looking for a cure for diabetes, Banting and Best would be impressed at how far their discovery has advanced and the contemporary knowledge that has been accumulated based on insulin action.

更新日期：2020-11-07

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