The responsiveness of the pancreas to glucose is assessed using the hyperglycemic clamp. Hyperglycemic clamps are performed on conscious mice with catheters chronically implanted in the jugular vein and carotid artery. A defined hyperglycemic stimulus is created using a primed variable glucose infusion to raise the glucose level to twice basal for 120 min. An established priming algorithm is used to elevate glucose quickly. Mice with extra copies of the glucokinase gene locus were demonstrated to have a blunted insulin response to hyperglycemia using this technique (Niswender et al. J. Biol. Chem. 1997).