Increased food intake with oxyntomodulin analogues.
Increased food intake with oxyntomodulin analogues.
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DOI：
10.1016/j.peptides.2015.09.006
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发表时间：
2015-11
期刊：
影响因子：
3
通讯作者：
Bloom SR
中科院分区：
文献类型：
--
作者：
Price SL;Minnion JS;Bloom SR
在大鼠中，OXM类似物在不减少食物摄入的情况下降低体重。在低OXM剂量下，食物摄入量通常增加。与Glu-3取代的GLP-1受体选择性类似物的比较。Glu-3肽组未观察到摄食量增加。表明胰高血糖素受体机制可能参与增加食物摄入。胃泌酸调节素类似物为肥胖症提供了新的治疗方法。然而，在大鼠模型中进行类似物筛选期间，始终观察到摄食量增加。为了进一步研究这一发现，将一系列代表性类似物（OXM 14和OXM 15）及其Glu-3等同物（OXM 14 E3和OXM 15 E3）给予大鼠7天，并进行食物摄入和体重测量。为了研究胰高血糖素受体活化的作用，在氨基酸位置3处取代谷氨酸（Glu/E）。在体外大鼠受体处测量胃泌酸调节肽类似物及其Glu-3对应物的GLP-1和胰高血糖素受体功效。25 nmol/kg的OXM 14和OXM 15的剂量使食物摄入增加高达20%。体重未显著增加。Glu-3肽未增加摄食量，表明胰高血糖素受体机制可能是摄食量增加的原因。
In rats OXM analogues decreased bodyweight without decreasing food intake. Food intake was often increased at low OXM doses. Comparison with Glu-3 substituted GLP-1 receptor selective analogues. No increase in food intake seen with Glu-3 peptides. Suggests a glucagon receptor mechanism may be involved in increasing food intake. Oxyntomodulin analogues offer a novel treatment for obesity. However during analogue screening in a rat model increased food intake was consistently observed. To further investigate this finding, a series of representative analogues (OXM14 and OXM15) and their Glu-3 equivalents (OXM14E3 and OXM15E3) were administered to rats for 7 days and food intake and bodyweight measurements taken. To investigate the role of glucagon receptor activation glutamate (Glu/E) was substituted at amino acid position 3. GLP-1 and glucagon receptor efficacy of the oxyntomodulin analogues and their Glu-3 counterparts were measured at the rat receptors in vitro. Doses of 25 n mol/kg of OXM14 and OXM15 increased food intake by up to 20%. Bodyweight was not significantly increased. Food intake was not increased with the Glu-3 peptides, indicating that a glucagon receptor mechanism may be responsible for the increase in food intake.