公开(公告)号：US06974671B1

公开(公告)日：2005-12-13

申请号：US10244045

申请日：2002-09-11

申请人： Marc R. Montminy ,  Bruce M. Spiegelman ,  Stephan Herzig

发明人： Marc R. Montminy ,  Bruce M. Spiegelman ,  Stephan Herzig

IPC分类号： C07H19/00 ,  C07H21/00 ,  C07H21/02 ,  C12Q1/68 ,  G01N33/00

CPC分类号： C07H19/00 ,  C07H21/00 ,  C07H21/02 ,  C12Q1/6897

摘要： In accordance with the present invention, it has been discovered that CREB regulates hepatic gluconeogenesis via the co-activator, PGC-1. PGC-1 potentiated glucocorticoid induction of the gene for PEPCK, the rate limiting enzyme in gluconeogenesis, via the glucocorticoid response unit in the promoter, indicating that activation of PGC-1 by CREB in liver contributes to the pathogenesis of diabetes mellitus. In accordance with the above discoveries, the present invention provides a method of identifying a compound that modulates gluconeogenesis. The invention method comprises contacting CREB and a nucleic acid comprising a PGC-1 promoter with a test compound, and determining if the test compound modulates binding between CREB and the PGC-1 promoter.

摘要翻译： 根据本发明，已经发现CREB通过共激活剂PGC-1调节肝糖异生。 通过启动子中的糖皮质激素反应单位，PGC-1增强糖皮质激素诱导的血浆生成中限速酶PEPCK的基因，表明肝脏中CREB对PGC-1的活化有助于糖尿病的发病。 根据上述发现，本发明提供了鉴定调节糖异生的化合物的方法。 本发明方法包括将CREB与包含PGC-1启动子的核酸与测试化合物接触，并确定测试化合物是否调节CREB与PGC-1启动子之间的结合。

公开(公告)号：US07220539B1

公开(公告)日：2007-05-22

申请号：US10462072

申请日：2003-06-12

申请人： Keyong Du ,  Stephan Herzig ,  Marc Montminy

发明人： Keyong Du ,  Stephan Herzig ,  Marc Montminy

IPC分类号： C12Q1/00 ,  C12N9/12 ,  C12N1/20 ,  C07K1/00 ,  C07H21/04

CPC分类号： C12N9/12 ,  C12N9/1205 ,  C12Q1/42 ,  C12Q1/48 ,  G01N2333/4721 ,  G01N2500/02

摘要： The present invention describes modulator of protein kinase B (PKB)/Akt proteins, exemplified by the Tribbles (TRB) family. An exemplary member of the TRB family, TRB-3, binds to Akt and inhibits its catalytic activity, in turn causing altered regulation of glucose metabolism pathways. TRB-3 expression is strongly induced in the fasting state, and upregulated in mouse models of type II, causing disruptions in insulin signaling. Accordingly, the present invention further provides compositions and methods for disrupting the interaction between such a modulator and PKB/Akt protein kinases. Also provided are methods of determining if a subject has a predisposition to impaired glucose regulation and methods for treating diabetes mellitus using invention compositions.

摘要翻译： 本发明描述了由Tribbles（TRB）家族举例说明的蛋白激酶B（PKB）/ Akt蛋白的调节剂。 TRB家族的示例性成员TRB-3与Akt结合并抑制其催化活性，反过来导致葡萄糖代谢途径的调节改变。 TRB-3表达在空腹状态下强烈诱导，并且在II型小鼠模型中上调，导致胰岛素信号传导中断。 因此，本发明还提供了用于破坏这种调节剂与PKB / Akt蛋白激酶之间相互作用的组合物和方法。 还提供了确定受试者是否具有受损的葡萄糖调节的倾向的方法以及使用本发明组合物治疗糖尿病的方法。