Glucose tolerance test
This test is commonly used to establish glucose tolerance, i.e. the ability to normalize the hyperglycaemic episode induced by the administration of a bolus of oral, intraperitoneal or intravenous glucose (depending on the study and the question asked) in rodents.
Insulin tolerance test
This test is used in rodents to assess insulin sensitivity. Hypoglycaemia induced by intraperitoneal or intravenous bolus insulin is an index of insulin sensitivity.
Tolerance tests involve a complex metabolic response that includes insulin secretion and/or insulin action. When a change in glucose tolerance or insulin sensitivity is suspected during these tests, a quantitative analysis of insulin secretion or insulin sensitivity can be performed using the hyperglycaemic clamp and the euglycaemic hyperinsulinaemic clamp, respectively.
Insulin secretion in hyperglycaemic clamp
The hyperglycaemic clamp is used to assess pancreatic beta cell function, i.e. insulin secretion in response to hyperglycaemia. The clamp is performed in alert, unrestrained animals. A glucose solution is infused through an intravenous catheter so as to maintain hyperglycaemia at 10, 15, or 20 mM (depending on the study). Blood glucose levels are measured by taking blood samples using an arterial catheter. During the test, various blood samples are drawn to establish the profile of plasma insulin and C-peptide levels over time.
Insulin sensitivity in euglycaemic hyperinsulinaemic clamp
The euglycaemic hyperinsulinaemic clamp enables insulin sensitivity to be measured quantitatively under conditions where glycaemia and hyperinsulinaemia are fixed at constant, measurable levels. The clamp is performed in alert, unrestrained animals. A glucose solution is infused intravenously at the same time as the insulin in order to maintain blood glucose levels at a target value (which varies depending on the study). The amount of glucose infused to maintain blood glucose levels in hyperinsulinaemic conditions is a direct measure of insulin sensitivity.