Mapping glucose-mediated gut-to-brain signalling pathways in humans.
Mapping glucose-mediated gut-to-brain signalling pathways in humans.
复制标题
绘制人类中葡萄糖介导的肠道到脑信号通路。
DOI：
10.1016/j.neuroimage.2014.03.059
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发表时间：
2014-08-01
期刊：
影响因子：
5.7
通讯作者：
McLaughlin JT
中科院分区：
文献类型：
--
作者：
Little TJ;McKie S;Jones RB;D'Amato M;Smith C;Kiss O;Thompson DG;McLaughlin JT
先前的fMRI研究已经证明，葡萄糖降低了人类下丘脑的BOLD反应。然而，中枢神经系统对葡萄糖反应的机制尚未确定。我们最近证明，葡萄糖对胃排空的减缓依赖于肠肽胆囊收缩素（CCK 1）受体的激活。本研究利用生理功能磁共振成像，旨在确定葡萄糖对全脑的反应，以及CCK是否起着中心作用。采用fMRI监测12名健康受试者在胃内输注（250 ml）以下药物后血氧水平依赖性（BOLD）信号的变化：1 M葡萄糖+右氧葡胺（CCK 1受体拮抗剂）预给药，1 M葡萄糖+安慰剂，或0.9%生理盐水（对照）+安慰剂，采用单盲、随机方式。测定胆囊体积、血糖、胰岛素、GLP-1和CCK浓度。还记录了饥饿、饱胀和恶心评分。胃内葡萄糖升高血浆葡萄糖、胰岛素和GLP-1，并减少胆囊体积（CCK分泌的体内测定）。与生理盐水相比，葡萄糖降低了脑干和下丘脑以及小脑、右枕叶皮质、壳核和丘脑的BOLD信号。BOLD信号下降的时间与血糖和胰岛素水平的升高呈负相关。葡萄糖+ dex臂突出了仅在运动皮层中BOLD信号的CCK 1受体依赖性增加。葡萄糖在人脑中诱导BOLD反应的位点特异性差异;脑干和下丘脑显示CCK 1受体非依赖性降低，这可能是由葡萄糖和胰岛素的循环效应介导的，而运动皮层显示早期右氧葡胺可逆的信号增加，表明CCK 1受体依赖性神经通路。我们已经确定了两种不同的中枢神经系统对葡萄糖的反应。CCK 1受体（CCK 1 R）依赖的BOLD信号在运动皮层增加。脑干和下丘脑中CCK 1 R非依赖性BOLD信号减少。BOLD信号的降低是由血糖和胰岛素的变化介导的，
Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250 ml) of: 1 M glucose + predosing with dexloxiglumide (CCK1 receptor antagonist), 1 M glucose + placebo, or 0.9% saline (control) + placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose + dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway. We have identified two distinct CNS responses to glucose in man. A CCK1 receptor (CCK1R)-dependent BOLD signal increase in the motor cortex. A CCK1R-independent BOLD signal decrease in the brainstem and hypothalamus. The BOLD signal decrease was mediated by changes in blood glucose and insulin,
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