ABSTRACT
Type 2 diabetes is a syndrome characterized by hyperglycemia, hyperinsulinemia, insulin resistance, and obesity. The effects of chronic hyperglycemia include many serious conditions such as atherosclerosis, nephropathy, neuropathy, retinopathy, and stroke. The increasing prevalence of type 2 diabetes has been attributed to the increasing obesity of the general population and consumption of a high-fat diet has been demonstrated to elicit the syndrome. In addition to promoting obesity, high-fat diets have been associated with risk for developing type 2 diabetes in epidemiological studies and, notably, this association has been found independent of obesity. Since obesity has been shown repeatedly (Morris et al., 1989; Marshall et al., 1991; Marshall et al., 1994; Feskens et al, 1995) to be one of the strongest risk markers for the development
of diabetes, high-fat diets may not only contribute directly to diabetes risk, but may also do so indirectly through their potential to induce obesity. An increase in dietary fat content has also been shown to produce diabetes and obesity in various strains of mice by West et al. (1992) and of rats by Schemmel et al. (1970). The C57BL/6J (B6) mouse has been wellcharacterized as an animal model to study the influence of diet on genetic background, specifically the genetics of diet-induced hyperinsulinemia, hyperglycemia, and obesity. The B6 mouse develops this syndrome only in response to a high-fat diet (Surwit et al., 1988). On a low-fat diet, this animal remains normal. In contrast, other strains such as the A/J mouse (Rebuffe-Scrive et al., 1993; Surwit et al., 1995; and Surwit et al, 1988) or the C57BL/KsJ (KsJ) (Surwit et al., 1994) are relatively resistant to these effects when fed a high fat diet. The A/J mouse has been used as a control strain throughout most of the research on the B6 mouse. The development of diabetes and obesity in the B6 mouse closely parallels the progression of common forms of the human disease. In humans, the onset of diabetes and obesity occurs gradually and often in the presence of a high-fat diet. In addition, Rebuffe-Scrive et al. (1993) and Surwit et al. (1995) reported that diet-induced diabetes and obesity in the B6 mouse is characterized by selective deposition of fat in the mesentery, an observation (Marshall et al., 1991 and Feskens et al,, 1995) consistent with the finding that abdominal obesity is an independent risk factor for diabetes in humans. Finally, Mills et al. (1993) reported that diet-induced diabetes and obesity in the B6 mouse is accompanied by the development of hypertension. Others have noted that high fat feeding can produce compromised immune function in B6 mice (Crevel et al., 1992).
