...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >A selective role for receptor activity-modifying proteins in subchronic action of the amylin selective receptor agonist NN1213 compared with salmon calcitonin on body weight and food intake in male mice
【24h】

A selective role for receptor activity-modifying proteins in subchronic action of the amylin selective receptor agonist NN1213 compared with salmon calcitonin on body weight and food intake in male mice

机译：与氨基素选择性受体激动剂NN1213的副矫正作用中受体活性改性蛋白质的选择性作用与鲑鱼降钙素对雄性小鼠的体重和食物摄入量相比

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The role of receptor activity-modifying proteins (RAMPs) in modulating the pharmacological effects of an amylin receptor selective agonist (NN1213) or the dual amylin-calcitonin receptor agonist (DACRA), salmon calcitonin (sCT), was tested in three RAMP KO mouse models, RAMP1, RAMP3 and RAMP1/3 KO. Male wild-type (WT) and knockout (KO) littermate mice were fed a 45% high-fat diet for 20 weeks prior to the 3-week treatment period. A decrease in body weight after NN1213 was observed in all WT mice, whereas sCT had no effect. The absence of RAMP1 had no significant effect on NN1213 efficacy, and sCT was still inactive. However, the absence of RAMP3 impeded NN1213 efficacy but improved sCT efficacy. Similar results were observed in RAMP1/3 KO suggesting that the amylin receptor 3 (AMY3 = CTR + RAMP3) is necessary for NN1213's maximal action on body weight and food intake and that the lack of AMY3 allowed sCT to be active. These results suggest that the chronic use of DACRA such as sCT can have unfavourable effect on body weight loss in mice (which differs from the situation in rats), whereas the use of the amylin receptor selective agonist does not. AMY3 seems to play a crucial role in modulating the action of these two compounds, but in opposite directions. The assessment of a long-term effect of amylin and DACRA in different rodent models is necessary to understand potential physiological beneficial and unfavourable effects on weight loss before its transition to clinical trials.
机译：受体活性修饰蛋白（RAMP）在调节胰淀素受体选择性激动剂（NN1213）或双胰淀素降钙素受体激动剂（DACRA）、鲑鱼降钙素（sCT）的药理作用中的作用在三种RAMP-KO小鼠模型RAMP1、RAMP3和RAMP1/3-KO中进行了测试。在为期3周的治疗期之前，雄性野生型（WT）和敲除型（KO）同窝小鼠被喂食45%的高脂肪饮食20周。在所有WT小鼠中观察到NN1213后体重下降，而sCT没有影响。RAMP1的缺失对NN1213的疗效没有显著影响，sCT仍然无效。然而，RAMP3的缺失阻碍了NN1213的疗效，但改善了sCT的疗效。在RAMP1/3 KO中观察到类似的结果，表明胰淀素受体3（AMY3=CTR+RAMP3）对于NN1213对体重和食物摄入的最大作用是必要的，并且缺乏AMY3允许sCT活跃。这些结果表明，长期使用DACRA（如sCT）会对小鼠的体重减轻产生不利影响（与大鼠的情况不同），而使用胰淀素受体选择性激动剂则不会。AMY3似乎在调节这两种化合物的作用中起着关键作用，但方向相反。在不同的啮齿类动物模型中评估胰淀素和达卡的长期效应，对于在过渡到临床试验之前了解其对减肥的潜在生理有利和不利影响是必要的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号