A novel model of type 2 diabetes mellitus based on obesity induced by high-fat diet in BDF1 mice.

Abstract

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.

• Authors: Hiroshi Karasawa, Seiko Nagata-Goto, Kiyosumi Takaishi, Yoshihiro Kumagae
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 58 Issue 3 Pg. 296-303 (Mar 2009) ISSN: 1532-8600 [Electronic] United States
• PMID: 19217442 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Dietary Fats
• Fatty Acids, Nonesterified
• Insulin
• Leptin
• Triglycerides
• Cholesterol

Topics

• Animals
• Blood Glucose (metabolism)
• Cholesterol (blood)
• Diabetes Mellitus, Type 2 (etiology)
• Dietary Fats
• Fatty Acids, Nonesterified (blood)
• Glucose Tolerance Test
• Glycosuria (urine)
• Insulin (metabolism)
• Insulin Secretion
• Islets of Langerhans (metabolism)
• Leptin (blood)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mice, Inbred Strains
• Models, Biological
• Obesity (complications)
• Triglycerides (blood)
• Weight Gain