The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes.
This study characterizes the high-fat diet-fed mouse as a model for impaired glucose tolerance (IGT) and type 2 diabetes. Female C57BL/6J mice were fed a high-fat diet (58% energy by fat) or a normal diet (11% fat). Body weight was higher in mice fed the high-fat diet already after the first week, due to higher dietary intake in combination with lower metabolic efficiency. Circulating glucose increased after 1 week on high-fat diet and remained elevated at a level of approximately 1 mmol/l throughout the 12-month study period. In contrast, circulating insulin increased progressively by time. Intravenous glucose challenge revealed a severely compromised insulin response in association with marked glucose intolerance already after 1 week. To illustrate the usefulness of this model for the development of new treatment, mice were fed an orally active inhibitor of dipeptidyl peptidase-IV (LAF237) in the drinking water (0.3 mg/ml) for 4 weeks. This normalized glucose tolerance, as judged by an oral glucose tolerance test, in association with augmented insulin secretion. We conclude that the high-fat diet-fed C57BL/6J mouse model is a robust model for IGT and early type 2 diabetes, which may be used for studies on pathophysiology and development of new treatment.
Winzell
Maria Sörhede
MS
Dept. of Medicine, Biomedical Center (BMC), B11, S-221 84 Lund, Sweden. maria.sorhede_winzell@medkem.lu.se
Ahrén
Bo
B
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000628:therapy*; D004041:Dietary Fats; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000628:therapy*; D005951:Glucose Tolerance Test; D051379:Mice; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000494:pharmacology
D001786:Blood Glucose; D004041:Dietary Fats; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4