Haeusler Rebecca A, McGraw Timothy E, Accili Domenico
Columbia University College of Physicians and Surgeons, Department of Pathology and Cell Biology, New York, New York 10032, USA.
Weill Cornell Medicine, Departments of Biochemistry and Cardiothoracic Surgery, New York, New York 10065, USA.
Nat Rev Mol Cell Biol. 2018 Jan;19(1):31-44. doi: 10.1038/nrm.2017.89. Epub 2017 Oct 4.
The mechanism of insulin action is a central theme in biology and medicine. In addition to the rather rare condition of insulin deficiency caused by autoimmune destruction of pancreatic β-cells, genetic and acquired abnormalities of insulin action underlie the far more common conditions of type 2 diabetes, obesity and insulin resistance. The latter predisposes to diseases ranging from hypertension to Alzheimer disease and cancer. Hence, understanding the biochemical and cellular properties of insulin receptor signalling is arguably a priority in biomedical research. In the past decade, major progress has led to the delineation of mechanisms of glucose transport, lipid synthesis, storage and mobilization. In addition to direct effects of insulin on signalling kinases and metabolic enzymes, the discovery of mechanisms of insulin-regulated gene transcription has led to a reassessment of the general principles of insulin action. These advances will accelerate the discovery of new treatment modalities for diabetes.
胰岛素作用机制是生物学和医学的核心主题。除了因胰腺β细胞自身免疫性破坏导致的极为罕见的胰岛素缺乏状况外，胰岛素作用的遗传和后天异常是2型糖尿病、肥胖症和胰岛素抵抗等更为常见病症的基础。后者易引发从高血压到阿尔茨海默病和癌症等一系列疾病。因此，了解胰岛素受体信号传导的生化和细胞特性无疑是生物医学研究的首要任务。在过去十年中，取得的重大进展已使葡萄糖转运、脂质合成、储存和动员机制得以明确。除了胰岛素对信号激酶和代谢酶的直接作用外，胰岛素调节基因转录机制的发现促使人们对胰岛素作用的一般原则进行重新评估。这些进展将加速糖尿病新治疗方法的发现。
