Adrenomedullin and glucagon-like peptide-1 have additive effects on food intake in mice
Adrenomedullin and glucagon-like peptide-1 have additive effects on food intake in mice
复制标题
DOI：
10.1016/j.biopha.2018.10.040
复制
发表时间：
2019-01-01
影响因子：
7.5
通讯作者：
Jelsing, Jacob
中科院分区：
文献类型：
--
作者：
Bech, Esben M.;Voldum-Clausen, Kristoffer;Jelsing, Jacob
肾上腺髓质素(adrenomedullin，ADM)是一种在多种外周器官表达的血管活性多肽，主要以其有益的血管活性作用而闻名。然而，ADM也可以抑制胰岛素的分泌，中央给药ADM已被证明会引起厌食效应。在这里，我们研究了外周联合应用ADM和胰升糖素样肽1(GLP-1)是否可以抑制ADM的降糖作用，同时增强其厌食特性。在雄性NMRI小鼠中，ADM和GLP-1单独和联合治疗12小时后，对食欲调节和血糖稳态的影响进行了尖锐的评估，同时通过口服葡萄糖耐量试验(OGTT)评估了对血糖稳态的影响。虽然单独使用GLP-1和ADM导致轻微的厌食作用，但两种多肽联合服用导致显著的食物摄入量减少。此外，单用ADM可显著增加OGTT诱发的血糖漂移，而ADM与较小剂量的GLP-1联合应用可使血糖漂移正常化。总之，我们证实了ADM和GLP-1的相加厌食作用，GLP-1联合应用可预防ADM诱导的糖耐量受损，提示ADM与GLP-1激动剂联合治疗可能成为潜在的减肥靶点。
Adrenomedullin (ADM) is a vasoactive peptide expressed in several peripheral organs and known primarily for its beneficial vasoactive effects. However, ADM is also known to inhibit insulin secretion, and central administration of ADM has been shown to elicit anorexigenic effects. Here, we investigated if peripheral co-administration of ADM and glucagon-like peptide 1 (GLP-1) could subdue the hypoglycaemic effects of ADM while enhancing its anorectic properties.The effects of mono-and combination therapy of ADM and GLP-1 on appetite regulation and glucose homeostasis were assessed acutely in male NMRI mice for 12 h, while effects on glucose homeostasis were assessed by oral glucose tolerance tests (OGTT).While the monotherapy with GLP-1 and ADM resulted in modest anorexigenic effects, co-administration of the two peptides led to a marked additive reduction in food intake. Moreover, while OGTT-evoked blood glucose-excursions were significantly increased by ADM monotherapy, co-administration of ADM with a lower dose of GLP-1 normalized glucose excursions.In conclusion, we demonstrate additive anorectic effects of ADM and GLP-1, and that GLP-1 co-administration prevents ADM-induced impairment of glucose tolerance, suggesting that ADM could be potential anti-obesity target when combined with GLP-1 agonist therapy.