For experimental research on
type 2 diabetes mellitus, a diet-induced
obesity-dependent diabetes model developed using genetically normal animals is essential. However, attempts at feeding a high-fat diet (HFD) to major inbred strains of mice have not resulted in the establishment of an ideal model. Here, we show that BDF1 mice, the F(1) hybrids of C57BL/6 and DBA/2 normal strains, develop HFD-induced
obesity-dependent diabetes. BDF1 mice fed a HFD gained weight rapidly and developed severe diabetes characterized by
hyperglycemia, glucosuria, and elevation of
hemoglobin A(1C) levels in 3 to 4 months. The
glucose tolerance of the diabetic mice was significantly impaired, and the elevation of plasma
insulin after a
glucose load was significantly reduced. Isolated pancreatic islets of HFD-fed BDF1 mice showed decreased
insulin content and a reduced
insulin secretory response to higher concentrations of
glucose. Immunohistochemical analysis of the pancreas showed reduced staining intensity to
insulin and aberrant distribution of
glucagon-positive cells in diabetic BDF1 mice. These observations suggest the cause of the diabetes in HFD-fed BDF1 mice to be dysfunction of the pancreatic beta-cells, which do not produce or secrete enough
insulin to compensate for
insulin resistance. BDF1 mice fed a HFD showing
obesity-dependent diabetes are suggested to be an appropriate animal model of
type 2 diabetes mellitus. This model would be useful for exploring the mechanism of
obesity-dependent
type 2 diabetes mellitus and evaluating antiobesity and
antidiabetic drugs.