Nandi Anindita, Kitamura Yukari, Kahn C Ronald, Accili Domenico
Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Physiol Rev. 2004 Apr;84(2):623-47. doi: 10.1152/physrev.00032.2003.
Insulin resistance plays a key role in the pathogenesis of several human diseases, including diabetes, obesity, hypertension, and cardiovascular diseases. The predisposition to insulin resistance results from genetic and environmental factors. The search for gene variants that predispose to insulin resistance has been thwarted by its genetically heterogeneous pathogenesis. However, using techniques of targeted mutagenesis and transgenesis in rodents, investigators have developed mouse models to test critical hypotheses on the pathogenesis of insulin resistance. Moreover, experimental crosses among mutant mice have shed light onto the polygenic nature of the interactions underlying this complex metabolic condition.
胰岛素抵抗在包括糖尿病、肥胖症、高血压和心血管疾病在内的多种人类疾病的发病机制中起着关键作用。胰岛素抵抗的易感性源于遗传和环境因素。由于其遗传异质性发病机制，寻找易导致胰岛素抵抗的基因变异一直受到阻碍。然而，通过在啮齿动物中使用靶向诱变和转基因技术，研究人员已经开发出小鼠模型来测试关于胰岛素抵抗发病机制的关键假设。此外，突变小鼠之间的实验杂交揭示了这种复杂代谢状况背后相互作用的多基因性质。
