Oxyntomodulin inhibits food intake in the rat
Oxyntomodulin inhibits food intake in the rat
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DOI：
10.1210/en.142.10.4244
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发表时间：
2001-10-01
期刊：
影响因子：
4.8
通讯作者：
Bloom, SR
中科院分区：
文献类型：
--
作者：
Dakin, CL;Gunn, I;Bloom, SR
泌酸调节素源自肠道和中枢神经系统中的胰高血糖素原加工过程。迄今为止，尚未证明其在中枢神经系统中的作用。我们在此报道，当脑室内和下丘脑室旁核注射到 24 小时禁食的大鼠时，胃泌酸调节素抑制再进食[脑室内和室旁核，1 小时，胃泌酸调节素（1 nmol），3.1 +/- 0.5 g；盐水，6.2 +/- 0.4 克； P<0.005]。此外，胃泌酸调节素可抑制在暗相开始时注射的非禁食大鼠的食物摄入（脑室注射，I h：胃泌酸调节素，3 nmol，1.1 +/- 0.19 g vs. 盐水，2.3 +/- 0.2 g；P < 0.05）。胃泌酸调节素对进食的影响与等摩尔剂量的胰高血糖素样肽-1 具有相似的时间过程和强度。研究的其他胰高血糖素原衍生产品[胰高血糖素、高血糖素（脑室内，3 nmol；室旁核，1 nmol）和间隔肽-1（脑室内和室旁核，3 nmol）]在任何检查时间点对喂养没有影响。当胃泌酸调节素（脑室内，3 nmol；进入室旁核，1 nmol）与胰高血糖素样肽-1受体拮抗剂 Exendin-(9-39)（脑室内，100 nmol；进入室旁核，10 nmol）共同给药时，其食欲作用被阻断。然而，与胰高血糖素样肽-1 相比，胃泌酸调节素对胰高血糖素样肽-1 受体的亲和力较低（IC50：胃泌酸调节素，8.2 nM，胰高血糖素样肽-1，0.16 nM）。对此的一种解释是，可能存在一种胃泌酸调节素受体，exendin-(9-39) 也可以与其结合并充当拮抗剂。
Oxyntomodulin is derived from proglucagon processing in the intestine and the central nervous system. To date, no role in the central nervous system has been demonstrated. We report here that oxyntomodulin inhibits refeeding when injected intracerebroventricularly and into the hypothalamic paraventricular nucleus of 24-h fasted rats [intracerebroventricularly and into the paraventricular nucleus, 1 h, oxyntomodulin (1 nmol), 3.1 +/- 0.5 g; saline, 6.2 +/- 0.4 g; P < 0.005]. In addition, oxyntomodulin inhibits food intake in nonfasted rats injected at the onset of the dark phase (intracerebroventricularly, I h: oxyntomodulin, 3 nmol, 1.1 +/- 0.19 g vs. saline, 2.3 +/- 0.2 g; P < 0.05). This effect of oxyntomodulin on feeding is of a similar time course and magnitude as that of an equimolar dose of glucagon-like peptide-1. Other proglucagon-derived products investigated [glucagon, glicentin (intracere-broventricularly, 3 nmol; into the paraventricular nucleus, 1 nmol), and spacer peptide-1 (intracerebroventricularly and into the paraventricular nucleus, 3 nmol)] had no effect on feeding at any time point examined. The anorectic effect of oxyntomodulin (intracerebroventricularly, 3 nmol; into the paraventricular nucleus, 1 nmol) was blocked when it was coadministered with the glucagon-like peptide-1 receptor antagonist, exendin-(9-39) (intracerebroventricularly, 100 nmol; into the paraventricular nucleus, 10 nmol). However, oxyntomodulin has a lower affinity for the glucagon-like peptide-1 receptor compared with glucagon-like peptide-1 (IC50: oxyntomodulin, 8.2 nM, glucagon-like peptide-1, 0.16 nM). One explanation for this is that there might be an oxyntomodulin receptor to which exendin-(9-39) can also bind and act as an antagonist.