Ayush Enkh-Amar, Iwasaki Yusaku, Iwamoto Sadahiko, Nakabayashi Hajime, Kakei Masafumi, Yada Toshihiko
Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
Division of Human Genetics, Center of Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
Biochem Biophys Res Commun. 2015 Jan 16;456(3):727-32. doi: 10.1016/j.bbrc.2014.12.031. Epub 2014 Dec 13.
Glucagon is released from the pancreatic islets postprandially and under hypoglycemic and cold conditions, and regulates glucose metabolism, feeding, energy expenditure and heat production, the functions partly controlled by the brain. Peripheral glucagon could signal to the brain via passing through the blood-brain barrier and/or acting on the vagal afferent. However, the latter remains to be determined. The present study aimed to clarify whether glucagon directly interacts with the nodose ganglion (NG) neurons of vagal afferent nerves in mice. In vivo study showed that intraperitoneal injection of glucagon induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), cellular activation makers, in NG neurons. In fura-2 microfluorometric studies, glucagon increased cytosolic Ca(2+) concentration ([Ca(2+)]i) in single NG neurons. The glucagon-induced [Ca(2+)]i increases were suppressed by a glucagon receptor antagonist, des-His(1)-[Glu(9)]-Glucagon (1-29) amide, and the glucagon receptor mRNA was expressed in NG neurons. The majority of glucagon-responsive NG neurons exhibited [Ca(2+)]i responses to insulin and cholecystokinin-8, the hormones that are secreted postprandially and implicated in satiety. These results demonstrate that glucagon, by interacting with the glucagon receptor, directly activates vagal afferent nerves, possibly being relayed to the signaling to the brain and formation of satiety.
胰高血糖素在餐后、低血糖和寒冷条件下从胰岛释放，调节葡萄糖代谢、进食、能量消耗和产热，这些功能部分受大脑控制。外周胰高血糖素可通过血脑屏障或作用于迷走神经传入纤维向大脑发出信号。然而，后者仍有待确定。本研究旨在阐明胰高血糖素是否直接与小鼠迷走神经传入纤维的结状神经节（NG）神经元相互作用。体内研究表明，腹腔注射胰高血糖素可诱导NG神经元中细胞外信号调节激酶1和2（ERK1/2）的磷酸化，ERK1/2是细胞活化标志物。在fura-2微荧光测定研究中，胰高血糖素可增加单个NG神经元的胞质Ca(2+)浓度（[Ca(2+)]i）。胰高血糖素受体拮抗剂des-His(1)-[Glu(9)]-胰高血糖素（1-29）酰胺可抑制胰高血糖素诱导的[Ca(2+)]i升高，且NG神经元中表达胰高血糖素受体mRNA。大多数对胰高血糖素反应的NG神经元对胰岛素和胆囊收缩素-8有[Ca(2+)]i反应，胰岛素和胆囊收缩素-8是餐后分泌且与饱腹感有关的激素。这些结果表明，胰高血糖素通过与胰高血糖素受体相互作用，直接激活迷走神经传入纤维，可能将信号传递至大脑并形成饱腹感。
