Department of Physiology, East Carolina University, Greenville, NC, USA.
J Pharmacol Exp Ther. 2012 Sep;342(3):631-6. doi: 10.1124/jpet.112.192146. Epub 2012 Jun 13.
The prevalence and economic burden of obesity and type 2 diabetes is a driving force for the discovery of molecular targets to improve insulin sensitivity and glycemic control. Here, we review several transgenic mouse models that identify promising targets, ranging from proteins involved in the insulin signaling pathway, alterations of genes affecting energy metabolism, and transcriptional metabolic regulators. Despite the diverse endpoints in each model, a common thread that emerges is the necessity for maintenance of energy balance, suggesting pharmacotherapy must target the development of drugs that decrease energy intake, accelerate energy expenditure in a well controlled manner, or augment natural compensatory responses to positive energy balance.
肥胖和 2 型糖尿病的流行率和经济负担是发现改善胰岛素敏感性和血糖控制的分子靶点的驱动力。在这里，我们回顾了几种转基因小鼠模型，这些模型确定了有前途的靶点，包括参与胰岛素信号通路的蛋白质、影响能量代谢的基因改变以及转录代谢调节剂。尽管每个模型的终点都不同，但一个共同的线索是需要维持能量平衡，这表明药物治疗必须针对开发减少能量摄入、以可控方式加速能量消耗或增强对正能量平衡的自然补偿反应的药物。
