The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

Figure 1

Tracer perfusion platform in the rat. Catheters were inserted into the tail artery and vein. This procedure used small incisions and enabled the rats to be kept conscious and relaxed throughout the experiment. It was constantly infused through the i.v. infusion line driven by a Harvard mini-infusion pump (Harvard Apparatus, Holliston, MA, USA) for 75 min (basal period). The infusion rates were 0.5 μCi/kg/min (3-³H-glucose) and 0.84 μmol/kg/min (U-¹³C-glycerol). Blood was sampled prior to infusion of tracer and at 65, 70, and 75 min. Subsequently, while the 3-³H-glucose infusion continued, a primed and continuous infusion of recombinant human insulin 5 mIu/kg/min was initiated for another 90 min. The plasma glucose concentration was kept constant at the basal level by monitoring the plasma glucose every 10 minutes and empirically adjusting the infusion rate of a 50% glucose solution. Twenty minutes before the end of the chase period, 1 μCi of 2-deoxy-D-¹⁴C-glucose was injected through the i.v. infusion line to enable measurement of tissue glucose uptake. During the final 10 minutes, 3 more blood samples were collected at 5-minute intervals.