Determination of progressive stages of type 2 diabetes in a 45% high-fat diet-fed C57BL/6J mouse model is achieved by utilizing both fasting blood glucose levels and a 2-hour oral glucose tolerance test

Abstract

Type 2 diabetes is considered one of the top ten life-threatening diseases worldwide. Following economic growth, obesity and metabolic syndrome became the most common risk factor for type 2 diabetes. In this regard, high-fat diet-fed C57BL/6J mouse model is widely used for type 2 diabetes pathogenesis and novel therapeutics development. However, criteria for classifying type 2 diabetes progressive stages in this mouse model are yet to be determined, led to the difficulty in experimental end-point decision. In this study, we fed C57BL/6J male mice with 45% high-fat diet, which is physiologically close to human high-fat consumption, and evaluated the progression of type 2 diabetes. After consuming high-fat diet for 4 weeks, mice developed metabolic syndrome, including obesity, significant increase of fasting plasma cholesterol level, elevation of both C-peptide and fasting blood glucose levels. By combining both fasting blood glucose test and 2-hour-oral glucose tolerance test, our results illustrated clear progressive stages from metabolic syndrome into pre-diabetes before onset of type 2 diabetes in C57BL/6J mice given a 45% high-fat diet. Besides, among metabolic measurements, accumulating body weight gain > 16.23 g for 12 weeks could be utilized as a potential parameter to predict type 2 diabetes development in C57BL/6J mice. Thus, these results might support future investigations in term of selecting appropriate disease stage in high-fat diet-fed C57BL/6J mouse model for studying early prevention and treatment of type 2 diabetes.