Since discovery, glucagon biology has remained enigmatic. Studies have shown that glucagon may have physiological effects beyond glucose regulation by binding to its receptor (Gcgr). The potential roles of glucagon and its receptor in the crosstalk between glucose metabolism and immune function of fish remain to be investigated. In the present study, we sequenced and characterized gcgra and gcgrb in grass carp. Phylogenetic analysis showed that they were highly homologous with their counterparts in fish. The gcgra and gcgrb mRNAs were ubiquitously expressed in all the tissues examined. The gcgra mRNA was highly expressed in the liver and gcgrb was mainly expressed in the liver and brain regions of grass carp. Furthermore, the results of oral glucose tolerance test (OGTT) showed that the expression levels of the two receptors were significantly increased at 12 h after treatment. In the hepatocytes, insulin inhibited gcgra and gcgrb mRNA expressions at 3−12 h and 6−12 h, respectively. While glucagon promoted their expressions at 3−12 h and 3 h, respectively. Intraperitoneal injection of lipopolysaccharide (LPS) increased hepatic gcgra mRNA level at 6 h post treatment, and up-regulated gcgrb mRNA abundance in the liver at 24 h. In response to polyinosinic polycytidylic acid [poly (I:C)] stimuli, however, gcgra and gcgrb mRNA levels were decreased. These results suggested that glucagon receptors were affected by bacterial-like and virus-like infection beyond their roles in the glucose metabolism of grass carp.

自发现以来，胰高血糖素生物学一直是个谜。研究表明，胰高血糖素可能通过结合其受体（Gcgr）而具有超出葡萄糖调节的生理作用。胰高血糖素及其受体在鱼的葡萄糖代谢和免疫功能之间的相互影响中的潜在作用仍有待研究。在本研究中，我们对草鱼中的gcgra和gcgrb进行了测序和鉴定。系统发育分析表明，它们与鱼类中的对应物高度同源。该gcgra和gcgrb的mRNA在所有组织中广泛表达检查。该gcgra基因在肝脏和中高表达gcgrb主要表达在草鱼的肝和脑区域。此外，口服葡萄糖耐量试验（OGTT）的结果表明，在治疗后12小时，两种受体的表达水平显着增加。在肝细胞中，胰岛素分别在3-12 h和6-12 h抑制gcgra和gcgrb mRNA表达。胰高血糖素分别在3-12 h和3 h促进其表达。腹腔注射脂多糖（LPS）在治疗后6小时可增加肝gcgra mRNA水平，并在24 h上调肝脏gcgrb mRNA的丰度。但是，响应多肌苷酸聚胞苷酸[poly（I：C）]刺激，gcgra和gcgrbmRNA水平降低。这些结果表明，胰高血糖素受体除了在草鱼的葡萄糖代谢中的作用外，还受到细菌样和病毒样感染的影响。