GPRC6A: Jack of all metabolism (or master of none).
GPRC6A: Jack of all metabolism (or master of none).
复制标题
GPRC6A：所有新陈代谢的杰克（或无主人）。
DOI：
10.1016/j.molmet.2016.12.006
复制
发表时间：
2017-02
影响因子：
8.1
通讯作者：
Quarles LD
中科院分区：
文献类型：
--
作者：
Pi M;Nishimoto SK;Quarles LD
GPRC 6A是一种广泛表达的G蛋白偶联受体，被认为是复杂内分泌网络和代谢过程的主要调节因子。GPRC 6A被多种配体激活，包括骨钙素（Ocn）、睾酮（T）、碱性氨基酸和各种阳离子。我们回顾了围绕GPRC 6A功能的争议。在小鼠中，GPRC 6A被提议通过激素的协调分泌来整合代谢功能，包括胰岛素、GLP-1、T和IL-6，以及该受体控制肝脏、骨骼肌和脂肪中的葡萄糖和脂肪代谢的直接作用。GPRC 6A的丢失导致代谢综合征（MetS），并且GPRC 6A的活化刺激β细胞的增殖，增加外周胰岛素敏感性，并且在大多数小鼠模型中保护免于高脂肪饮食（HFD）诱导的代谢异常。GPRC 6A的骨、心血管、免疫和皮肤功能也已在小鼠中鉴定。GPRC 6A的表达在前列腺癌（PCa）细胞中增加，并且GPRC 6A的抑制在小鼠模型中减弱PCa进展。然而，GPRC 6A在人类中的功能尚不清楚。在进化过程中，GPRC 6A的独特多态性主要出现在亚洲人和欧洲人中，已经提出改变膜运输和功能。相比之下，在所有其他物种中发现的祖先等位基因分别保留在1%，15%和40%的亚洲人，欧洲人和非洲人后裔中，这表明GPRC 6A基因变异可能导致发生MetS和PCa风险的种族差异。如果在小鼠中鉴定的GPRC 6A的调节功能转化为人类，并且发现GPRC 6A的多态性预测人类疾病的种族差异，那么GPRC 6A可能是预测，预防和治疗MetS，PCa和其他受GPRC 6A影响的疾病的新基因靶点。
GPRC6A, a widely expressed G-protein coupled receptor, is proposed to be a master regulator of complex endocrine networks and metabolic processes. GPRC6A is activated by multiple ligands, including osteocalcin (Ocn), testosterone (T), basic amino acids, and various cations. We review the controversy surrounding GPRC6A functions. In mice, GPRC6A is proposed to integrate metabolic functions through the coordinated secretion of hormones, including insulin, GLP-1, T, and IL-6, and direct effects of this receptor to control glucose and fat metabolism in the liver, skeletal muscle, and fat. Loss-of-GPRC6A results in metabolic syndrome (MetS), and activation of GPRC6A stimulates proliferation of β-cells, increases peripheral insulin sensitivity, and protects against high fat diet (HFD) induced metabolic abnormalities in most mouse models. Bone, cardiovascular, immune, and skin functions of GPRC6A have also been identified in mice. Expression of GPRC6A is increased in prostate cancer (PCa) cells, and inhibition of GPRC6A attenuates PCa progression in mouse models. The function of GPRC6A in humans, however, is not clear. During evolution, a unique polymorphism of GPRC6A emerged mainly in humans of Asian and European decent that has been proposed to alter membrane trafficking and function. In contrast, the ancestral allele found in all other species is retained in 1%, 15%, and 40% of people of Asian, European and African descent, respectively, suggesting GPRC6A gene variants may contribute to the racial disparities in the risk of developing MetS and PCa. If the regulatory functions of GPRC6A identified in mice translate to humans, and polymorphisms in GPRC6A are found to predict racial disparities in human diseases, GPRC6A may be a new gene target to predict, prevent, and treat MetS, PCa, and other disorders impacted by GPRC6A.