The beta-cell in type 2 diabetes and in obesity.

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.