Glucose-dependent insulinotropic polypeptide receptor (GIPR) is associated with obesity in human genome-wide association studies. Similarly, mouse genetic studies indicate that loss of function alleles and glucose-dependent insulinotropic polypeptide overexpression both protect from high-fat diet-induced weight gain. Together, these data provide compelling evidence to develop therapies targeting GIPR for the treatment of obesity. Further, both antagonists and agonists alone prevent weight gain, but result in remarkable weight loss when codosed or molecularly combined with glucagon-like peptide-1 analogs preclinically. Here, we review the current literature on GIPR, including biology, human and mouse genetics, and pharmacology of both agonists and antagonists, discussing the similarities and differences between the 2 approaches. Despite opposite approaches being investigated preclinically and clinically, there may be viability of both agonists and antagonists for the treatment of obesity, and we expect this area to continue to evolve with new clinical data and molecular and pharmacological analyses of GIPR function.

中文翻译：

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糖尿病患者的葡萄糖依赖性促胰岛素多肽受体疗法，激动剂=拮抗剂吗？

在人类全基因组关联研究中，葡萄糖依赖性促胰岛素多肽受体（GIPR）与肥胖症相关。同样，小鼠遗传研究表明，功能等位基因的缺失和葡萄糖依赖性促胰岛素多肽的过度表达均可以防止高脂饮食诱导的体重增加。这些数据加在一起，为开发针对GIPR的肥胖症治疗方法提供了令人信服的证据。此外，拮抗剂和激动剂都单独防止体重增加，但是在临床前与胰高血糖素样肽-1类似物共剂量或分子结合时，会导致明显的体重减轻。在这里，我们回顾了有关GIPR的最新文献，包括生物学，人类和小鼠遗传学以及激动剂和拮抗剂的药理学，讨论了这两种方法之间的异同。