Deletion of the G Protein-Coupled Receptor 30 Impairs Glucose Tolerance, Reduces Bone Growth, Increases Blood Pressure, and Eliminates Estradiol-Stimulated Insulin Release in Female Mice
Deletion of the G Protein-Coupled Receptor 30 Impairs Glucose Tolerance, Reduces Bone Growth, Increases Blood Pressure, and Eliminates Estradiol-Stimulated Insulin Release in Female Mice
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DOI：
10.1210/en.2008-0623
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发表时间：
2009-02-01
期刊：
影响因子：
4.8
通讯作者：
Leeb-Lundberg, L. M. Fredrik
中科院分区：
文献类型：
--
作者：
Martensson, Ulrika E. A.;Salehi, S. Albert;Leeb-Lundberg, L. M. Fredrik
体外研究表明G蛋白偶联受体（GPR） 30是一种功能性雌激素受体。然而，GPR30在体内的生理作用尚不清楚，GPR30在体内是否也是雌激素受体尚不清楚。为此，我们研究了破坏GPR30基因对雌性和雄性小鼠的影响。雌性GPR30（(-/-)）小鼠出现高血糖和糖耐量受损，身体生长减慢，血压升高，血清IGF-I水平降低。生长的减少与骨骼发育的比例减少相关。血压升高与血管阻力增加有关，表现为阻力动脉的介质与管腔比增加。体内高血糖和糖耐量受损与体内和体外离体胰岛胰岛素表达和释放减少有关。GPR30在胰岛中表达，GPR30的缺失在体内和体外离体胰岛中都能消除雌二醇刺激的胰岛素释放。我们的研究结果表明，GPR30对雌性小鼠的几种代谢功能很重要，包括雌二醇刺激的胰岛素释放。（内分泌学150:687-698,2009）
In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release. (Endocrinology 150: 687-698, 2009)