CREB regulates hepatic gluconeogenesis through the coactivator PGC-1

When mammals fast, glucose homeostasis is achieved by triggering expression of gluconeogenic genes in response to glucagon and glucocorticoids. The pathways act synergistically to induce gluconeogenesis (glucose synthesis), although the underlying mechanism has not been determined. Here we show that mice carrying a targeted disruption of the cyclic AMP (cAMP) response element binding (CREB) protein gene, or overexpressing a dominant-negative CREB inhibitor, exhibit fasting hypoglycaemia [corrected] and reduced expression of gluconeogenic enzymes. CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo. Overexpression of PGC-1 in CREB-deficient mice restored glucose homeostasis and rescued expression of gluconeogenic genes. In transient assays, PGC-1 potentiated glucocorticoid induction of the gene for phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in gluconeogenesis. PGC-1 promotes cooperativity between cyclic AMP and glucocorticoid signalling pathways during hepatic gluconeogenesis. Fasting hyperglycaemia is strongly correlated with type II diabetes, so our results suggest that the activation of PGC-1 by CREB in liver contributes importantly to the pathogenesis of this disease.     

百脉根Rac1基因启动子的克隆与表达分析

百脉根小G蛋白Rac1基因促进共生结瘤过程,但其转录调控机制尚不明确.采用生物信息学方法对百脉根Rac1基因的启动子序列进行了预测,并对该启动子中含有的顺式调控元件进行了统计分析.克隆了约1.8kb的启动子片段,并构建了GUS融合的重组质粒p1391Z-Rac1Pro.通过百脉根毛根转化法获得转基因毛根,进一步利用组织化学染色法对Rac1基因在阳性毛根中的表达部位进行了研究.结果显示:该启动子除含有常见的转录调控保守元件TATA-box和CAAT-box外,还含有调控防御和胁迫、激素、光照等信号的应答元件.组织化学染色发现,Rac1基因在接种根瘤菌的根毛、根尖、根瘤原基皮层中表达量较高.