首页 | 本学科首页   官方微博 | 高级检索  
     


An integrated functional genomics screening program reveals a role for BMP-9 in glucose homeostasis
Authors:Chen Cecil  Grzegorzewski Krzysztof J  Barash Steve  Zhao Qinghai  Schneider Helmut  Wang Qi  Singh Mallika  Pukac Laurie  Bell Adam C  Duan Roxanne  Coleman Tim  Duttaroy Alokesh  Cheng Susan  Hirsch Jon  Zhang Linyi  Lazard Yanick  Fischer Carrie  Barber Melisa Carey  Ma Zhi-Dong  Zhang Ya-Qin  Reavey Peter  Zhong Lilin  Teng Baiqin  Sanyal Indra  Ruben Steve M  Blondel Olivier  Birse Charles E
Affiliation:Department of Lead Development and Characterization, Human Genome Sciences, Inc., 9800 Medical Center Dr., Rockville, MD 20850, USA.
Abstract:
A coordinated functional genomics program was implemented to identify secreted polypeptides with therapeutic applications in the treatment of diabetes. Secreted factors were predicted from a diverse expressed-sequence tags (EST) database, representing >1,000 cDNA libraries, using a combination of bioinformatic algorithms. Subsequently, approximately 8,000 human proteins were screened in high-throughput cell-based assays designed to monitor key physiological transitions known to be centrally involved in the physiology of type 2 diabetes. Bone morphogenetic protein-9 (BMP-9) gave a positive response in two independent assays: reducing phosphoenolpyruvate carboxykinase (PEPCK) expression in hepatocytes and activating Akt kinase in differentiated myotubes. Purified recombinant BMP-9 potently inhibited hepatic glucose production and activated expression of key enzymes of lipid metabolism. In freely fed diabetic mice, a single subcutaneous injection of BMP-9 reduced glycemia to near-normal levels, with maximal reduction observed 30 hours after treatment. BMP-9 represents the first hepatic factor shown to regulate blood glucose concentration. Using a combination of bioinformatic and high-throughput functional analyses, we have identified a factor that may be exploited for the treatment of diabetes.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号