Nutritional models of type 2 diabetes mellitus.

In order to better understand the events which precede and precipitate the onset of type 2 diabetes (T2DM) several nutritional animal models have been developed. These models are generated by manipulating the diet of either the animal itself or its mother during her pregnancy and, in comparison to traditional genetic and knock out models, have the advantage that they more accurately reflect the aetiology of human T2DM. This chapter will discuss some of the most widely used nutritional models of T2DM: Diet-induced obesity (DIO) in adult rodents, and studies of prenatal and postnatal nutrition in offspring of mothers fed a low-protein diet or overnourished during pregnancy. Several common mechanisms have been identified through which these nutritional manipulations can lead to metabolic disease, including pancreatic beta-cell dysfunction, impaired insulin signalling in skeletal muscle and the excess accumulation of visceral adipose tissue and consequent deposition of non-esterified fatty acids in peripheral tissues resulting in peripheral insulin resistance. The following chapter will discuss each of these nutritional models, their application and relationship to human aetiology, and will highlight the important insights these models have provided into the pathogenesis of T2DM.