Rutter Guy A, Parton Laura E
Department of Cell Biology, Division of Medicine, Imperial College London, London, UK.
Front Horm Res. 2008;36:118-134. doi: 10.1159/000115360.
The current worldwide epidemic of obesity and metabolic diseases has energised the search for new approaches to treat these conditions. Type 2 diabetes appears to involve an interplay between susceptible genetic backgrounds and environmental factors including highly calorific westernised diets. The latter may generate 'glucolipotoxic' conditions which affect both the pancreatic beta-cell and insulin-sensitive tissues. Here we focus on efforts to better understand the basic signalling mechanisms through which the beta-cell senses changes in glucose concentration and how this process may become defective in type 2 diabetes. The recent demonstrations, through whole genome association studies, of important roles for genes involved in the control of cell cycle, as well as intracellular ion homeostasis, further highlight the central role of the beta-cell in both the pathogenesis of the disease and as a therapeutic target.
当前全球范围内肥胖症和代谢性疾病的流行促使人们寻找治疗这些疾病的新方法。2型糖尿病似乎涉及易感基因背景与环境因素之间的相互作用，这些环境因素包括高热量的西式饮食。后者可能会产生“糖脂毒性”状态，影响胰腺β细胞和胰岛素敏感组织。在这里，我们重点关注为更好地理解β细胞感知葡萄糖浓度变化的基本信号传导机制，以及该过程在2型糖尿病中可能如何出现缺陷所做的努力。最近通过全基因组关联研究表明，参与细胞周期控制以及细胞内离子稳态的基因具有重要作用，这进一步凸显了β细胞在疾病发病机制和作为治疗靶点方面的核心作用。
