Nutritional Models of Type 2 Diabetes Mellitus

In order to better understand the events that 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 etiology 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 offspring of mothers fed a low-protein, high-fat and/or high-sugar diet during pregnancy and/or lactation. Several common mechanisms have been identified through which these nutritional manipulations can lead to metabolic disease, including pancreatic beta-cell dysfunction, impaired insulin signaling in skeletal muscle, and the excess accumulation of visceral adipose tissue and consequent deposition of nonesterified fatty acids in peripheral tissues. In addition, there is an emerging concept that obesity/poor quality diets result in increased production and release of pro-inflammatory cytokines from adipose tissue leading to a state of chronic low-grade inflammation, and that this is likely to represent an important link between obesity/diet and metabolic dysfunction. The following chapter will discuss the most common nutritional models of T2DM in experimental animals, their application, and relationship to human etiology, and will highlight the important insights these models have provided into the pathogenesis of T2DM.