The glucose tolerance test is used in the clinic as well as clinical and basic research to identify individuals with impaired glucose tolerance. Because of its simplicity, it is the most commonly used physiological test for the assessment of glucose homeostasis in rodents. The glucose tolerance test measures the clearance of an intraperitoneally injected glucose load from the body. It is used to detect impairment in glucose metabolism that can be linked to conditions, such as diabetes, obesity, cardiovascular diseases, and metabolic syndromes. Glucose intolerance is caused by insulin resistance in peripheral metabolic tissues and by impaired glucose-stimulated insulin secretion.
The standard protocol includes either overnight fasting or fasting for 5-6 h before the test. After fasting, blood is taken from a tail cut and baseline glucose levels are measured. Subsequently, a single dose of a 20 % glucose solution is applied intraperitoneally before additional blood glucose concentration measurements at 15, 30, 60, and 120 min post-injection are performed. Glucose is measured with a glucometer that is calibrated before testing. Although both fasting protocols are generally accepted, the intermittent fasting protocol for 5-6 h is preferred for two reasons. First, overnight fasting can lead to a decrease in body weight that is larger than advised, and second, due to the difference in size and metabolic rate between humans and rodents, the results obtained after 5-6 h of fasting in rodents, best resembles protocols used in humans. It is important to note that differences between sexes and strains can appear already at baseline.
The glucose tolerance test is commonly used in combination with the insulin tolerance test.
Figure: Assessment of glucose tolerance in C57BL/6 mice treated with high fat diet for 12 weeks. Blood glucose level measurements per group measured at baseline (A), after 6 weeks (B) and 12 weeks (C) of high fat/control diet. Mean ± SEM. n = 10 per group. Two-way ANOVA with Bonferroni´s post hoc test. *p<0.05; ***p<0.001.