Pancreatic β-Cells Communicate With Vagal Sensory Neurons.
Pancreatic β-Cells Communicate With Vagal Sensory Neurons.
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DOI：
10.1053/j.gastro.2020.10.034
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发表时间：
2021-02
期刊：
影响因子：
29.4
通讯作者：
中科院分区：
文献类型：
--
作者：
破坏内脏感觉神经会影响胰岛功能、糖代谢和糖尿病发病，但胰岛内分泌细胞如何与感觉神经元相互作用尚未研究。我们通过结合病毒示踪、免疫组织化学和报告小鼠模型来表征胰腺感觉神经支配的解剖模式。为了评估β细胞与迷走神经感觉神经元的功能相互作用，我们在体内记录了单个结状神经元中的Ca 2+反应，同时用化学发生学和药理学方法选择性地刺激β细胞。我们发现，胰岛神经支配的迷走神经感觉轴突表达Phox 2b，P物质，降钙素基因相关肽，和5-羟色胺受体5 HT 3R。在中枢，迷走神经元投射到胰腺终止于孤束连合核。结状神经元在体内对β细胞的化学刺激和胰腺输注5-羟色胺有反应，但对胰岛素不敏感。对β细胞的化学发生和药理学刺激的反应被5 HT 3R拮抗剂阻断，并通过增加β细胞中的5-羟色胺水平而增强。我们进一步直接在活胰腺切片中证实，胰岛中的感觉末梢对5-羟色胺敏感。我们的研究表明，胰腺β细胞与迷走神经感觉神经元进行交流，可能使用5-羟色胺信号转导机制。5-羟色胺与胰岛素共同释放，因此可以通过迷走传入神经传递有关β细胞分泌状态的信息。我们的研究证实，胰腺的胰岛素分泌β细胞与迷走神经的感觉神经元通信，迷走神经又将此信息传递给大脑。
Destroying visceral sensory nerves impacts pancreatic islet function, glucose metabolism and diabetes onset, but how islet endocrine cells interact with sensory neurons has not been studied. We characterized the anatomical pattern of pancreatic sensory innervation by combining viral tracing, immunohistochemistry, and reporter mouse models. To assess the functional interactions of beta cells with vagal sensory neurons, we recorded Ca2+ responses in individual nodose neurons in vivo while selectively stimulating beta cells with chemogenetic and pharmacologic approaches. We found that pancreatic islets are innervated by vagal sensory axons expressing Phox2b, substance P, calcitonin-gene related peptide, and the serotonin receptor 5HT3R. Centrally, vagal neurons projecting to the pancreas terminate in the commissural nucleus of the solitary tract. Nodose neurons responded in vivo to chemogenetic stimulation of beta cells and to pancreas infusion with serotonin, but were not sensitive to insulin. Responses to chemogenetic and pharmacological stimulation of beta cells were blocked by a 5HT3R antagonist and were enhanced by increasing serotonin levels in beta cells. We further confirmed directly in living pancreas slices that sensory terminals in the islet were sensitive to serotonin. Our study establishes that pancreatic beta cells communicate with vagal sensory neurons, likely using serotonin signaling as a transduction mechanism. Serotonin is co-released with insulin and may therefore convey information about the secretory state of beta cells via vagal afferent nerves. Our study established that insulin secreting beta cell of the pancreas communicate with sensory neurons of the vagus nerve, which in turns relay this information to the brain.
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影响因子：
3.7
作者：
Iwasaki Y;Shimomura K;Kohno D;Dezaki K;Ayush EA;Nakabayashi H;Kubota N;Kadowaki T;Kakei M;Nakata M;Yada T
通讯作者：
Yada T
影响因子：
2.5
作者：
CAROBI, C
通讯作者：
CAROBI, C
影响因子：
64.5
作者：
Chang RB;Strochlic DE;Williams EK;Umans BD;Liberles SD
通讯作者：
Liberles SD
影响因子：
64.5
作者：
Bellono NW;Bayrer JR;Leitch DB;Castro J;Zhang C;O'Donnell TA;Brierley SM;Ingraham HA;Julius D
通讯作者：
Julius D
影响因子：
3.4
作者：
Gram, Dorte X.;Ahren, Bo;Hansen, Anker J.
通讯作者：
Hansen, Anker J.