Insulin in the brain: there and back again.
Insulin in the brain: there and back again.
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DOI：
10.1016/j.pharmthera.2012.07.006
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发表时间：
2012-10
影响因子：
13.5
通讯作者：
Erickson, Michelle A.
中科院分区：
文献类型：
--
作者：
Banks, William A.;Owen, Joshua B.;Erickson, Michelle A.
胰岛素在中枢神经系统中发挥独特的功能。胰岛素几乎完全由胰腺产生，使用可饱和转运蛋白穿过血脑屏障（BBB），通过CNS机制影响进食和认知，在很大程度上不依赖于葡萄糖利用。外周胰岛素主要作为代谢调节激素发挥作用，而中枢胰岛素对大脑的一系列作用可能更接近于祖先胰岛素分子的作用。脑内皮细胞（BEC）是形成血管BBB的细胞，含有将胰岛素从血液转运到脑的转运蛋白，其本身受胰岛素调节。胰岛素转运蛋白的改变是由生理和病理因素，包括高血糖症和糖尿病状态。后者可能导致BBB中断。周细胞，与BEC密切接触的多能细胞，保护BBB的完整性及其运输胰岛素的能力。大多数胰岛素在CNS内的已知作用是通过两种典型途径介导的，即磷酸肌醇-3激酶（PI 3）/Akt和Ras/丝裂原活化激酶（MAPK）级联。中枢神经系统内的胰岛素抵抗，有时称为III型糖尿病，与外周胰岛素抵抗有关，但也可能存在可变激素抵抗综合征，因此一个组织床的抵抗可能与其他组织床的抵抗无关。中枢神经系统胰岛素抵抗与阿尔茨海默病、抑郁症和妊娠期压力感受器增益受损有关。CNS胰岛素作用的这些方面和BBB对其进入的控制可能只是胰岛素在脑内的故事的一小部分。
Insulin performs unique functions within the CNS. Produced nearly exclusively by the pancreas, insulin crosses the blood-brain barrier (BBB) using a saturable transporter, affecting feeding and cognition through CNS mechanisms largely independent of glucose utilization. Whereas peripheral insulin acts primarily as a metabolic regulatory hormone, CNS insulin has an array of effects on brain that may more closely resemble the actions of the ancestral insulin molecule. Brain endothelial cells (BEC), the cells that form the vascular BBB and contain the transporter that translocates insulin from blood to brain, is itself regulated by insulin. The insulin transporter is altered by physiological and pathological factors including hyperglycemia and the diabetic state. The latter can lead to BBB disruption. Pericytes, pluripotent cells in intimate contact with the BEC, protect the integrity of the BBB and its ability to transport insulin. Most of insulin’s known actions within the CNS are mediated through two canonical pathways, the phosphoinositide-3 kinase (PI3)/Akt and Ras/mitogen activated kinase (MAPK) cascades. Resistance to insulin action within the CNS, sometimes referred to as diabetes mellitus type III, is associated with peripheral insulin resistance, but it is possible that variable hormonal resistance syndromes exist so that resistance at one tissue bed may be independent of that at others. CNS insulin resistance is associated with Alzheimer’s disease, depression, and impaired baroreceptor gain in pregnancy. These aspects of CNS insulin action and the control of its entry by the BBB are likely only a small part of the story of insulin within the brain.
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影响因子：
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