The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic
The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic
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DOI：
10.2337/diabetes.51.12.3412
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发表时间：
2002-12-01
期刊：
影响因子：
7.7
通讯作者：
Dickson, SL
中科院分区：
文献类型：
--
作者：
Hewson, AK;Tung, LYC;Dickson, SL
控制食物摄入和体重的下丘脑回路接收并整合来自循环饱腹感信号的信息，例如瘦素和胰岛素，以及来自生长激素释放肽的信息，生长激素释放肽是唯一已知的在全身注射后刺激食欲的循环激素。与喂食大鼠相比，48 h禁食大鼠中由生长激素释放肽和生长激素释放肽模拟物（生长激素促分泌素）激活的弓状神经元增加，这反映在响应于相同最大有效剂量的给药而表达Fos蛋白的细胞数量更大。因此，我们试图确定这种增加的反应是否反映了低水平的循环饱腹感因子，如瘦素或胰岛素，或受其影响。慢性中央输注胰岛素或瘦素在48小时的快速抑制Fos反应的三倍增加静脉注射的最大有效剂量的生长激素释放肽（GHRP）-6，合成生长激素促分泌素。这似乎是胰岛素和瘦素的直接中枢作用，因为空腹期间胰岛素、瘦素和葡萄糖的血浆水平的显著降低不受任一激素的中枢给药的影响。此外，GHRP-6诱导的Fos反应是肥胖的瘦素和胰岛素抵抗Zucker大鼠的两倍，与瘦对照组相比。这些数据提供的证据表明，生长激素释放肽敏感的电路在下丘脑的动态调节中枢胰岛素和瘦素的行动。
The hypothalamic circuits controlling food intake and body weight receive and integrate information from circulating satiety signals such as leptin and insulin and also from ghrelin, the only known circulating hormone that stimulates appetite following systemic injection. Activation of arcuate neurons by ghrelin and ghrelin mimetics (the growth hormone secretagogues) is augmented in 48-h-fasted rats compared with fed rats, as reflected by a greater number of cells expressing Fos protein in response to administration of the same maximally effective dose. Hem we sought to determine whether this increased responsiveness in fasting might reflect or be influenced by low levels of circulating satiety factors such as leptin or insulin. Chronic central infusion of insulin or leptin during a 48-h fast suppressed the threefold increase in the Fos response to intravenous injection of a maximally effective dose of growth hormone-releasing peptide (GHRP)-6, a synthetic growth hormone secretagogue. This appears to be a direct central action of insulin and leptin because the marked decrease in plasma levels of insulin, leptin, and glucose during fasting were unaffected by central administration of either hormone. Furthermore, the GHRP-6-induced Fos response was twofold greater in obese leptin- and insulin-resistant Zucker rats compared with lean controls. These data provide evidence that the ghrelin-sensitive circuits in the hypothalamus are dynamically regulated by central insulin and leptin action.