Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling
Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling
复制标题
DOI：
10.1074/jbc.m009382200
复制
发表时间：
2001-06-15
影响因子：
4.8
通讯作者：
Drucker, DJ
中科院分区：
文献类型：
--
作者：
Lovshin, J;Estall, J;Drucker, DJ
胰高血糖素样肽-2（GLP-2）通过影响营养吸收和维持肠粘膜上皮完整性来调节能量稳态。GLP-2在中枢神经系统（CNS）中的生物学作用仍然知之甚少。我们研究了内源性GLP-2受体（GLP-2 R）表达的位点，小鼠GLP-2 R启动子控制下转基因LacZ表达的定位，以及GLP-2在小鼠CNS中的作用，在小鼠和大鼠CNS的多个下丘脑外区域检测到GLP-2 R表达，包括小脑，延髓，杏仁核，海马，齿状回，笔，大脑皮质，和垂体，小鼠GLP-2 R启动子的1.5-磷酸酶片段指导LacZ在小鼠胃肠道和CNS区域表达，这些区域表现出内源性GLP-2 R表达，包括小脑、杏仁核、海马和齿状回。侧脑室注射GLP-2显著抑制野生型小鼠在黑暗期进食期间的食物摄入。在野生型小鼠或GLP-1 R（-/-）小鼠中，用拮抗剂exendin-（9-39）破坏胰高血糖素样肽-1受体（GLP-1 R）信号传导可显著增强GLP-2的厌食作用，这些发现说明CNS GLP-2 R表达并不局限于下丘脑核团，并证明GLP-2 R的厌食作用与下丘脑核团中GLP-2 R的表达有关。2是瞬时的，并通过体内GLP-1 R信号传导的存在或不存在来调节。
Glucagon-like peptide-2 (GLP-2) regulates energy homeostasis via effects on nutrient absorption and maintenance of gut mucosal epithelial integrity. The biological actions of GLP-2 in the central nervous system (CNS) remain poorly understood. We studied the sites of endogenous GLP-2 receptor (GLP-2R) expression, the localization of transgenic LacZ expression under the control of the mouse GLP-2R promoter, and the actions of GLP-2 in the murine CNS, GLP-2R expression was detected in multiple extrahypothalamic regions of the mouse and rat CNS, including cell groups in the cerebellum, medulla, amygdala, hippocampus, dentate gyrus, pens, cerebral cortex, and pituitary, A 1.5-kilobase fragment of the mouse GLP-2R promoter directed LacZ expression to the gastrointestinal tract and CNS regions in the mouse that exhibited endogenous GLP-2R expression, including the cerebellum, amygdala, hippocampus, and dentate gyrus, Intracerebroventricular injection of GLP-2 significantly inhibited food intake during dark-phase feeding in wild-type mice. Disruption of glucagonlike peptide-1 receptor (GLP-1R) signaling with the antagonist exendin-(9-39) in wild-type mice or genetically in GLP-1R(-/-) mice significantly potentiated the anorectic actions of GLP-2, These findings illustrate that CNS GLP-2R expression is not restricted to hypothalamic nuclei and demonstrate that the anorectic effects of GLP-2 are transient and modulated by the presence or absence of GLP-1R signaling in vivo.