The insulin status of sheep with genetic differences in glucose clearance

Lines of sheep have been selected for Slow or Fast glucose clearance after a glucose tolerance test. The aim of this work was to establish what characteristics of the insulin status were altered by the breeding program. Six animals from each line with consistently Slow (T-half > 70 min) or Fast (T-half < 60 min) decreases in plasma glucose concentration were studied in three different experiments. After the injection of [125I]insulin, blood was sampled for 300 min. The change in radioactivity with time was used in a three-compartment series model to estimate theoretical insulin pool sizes and flow rates between pools. All three pools were significantly (P < 0.05) larger in the Slow (61, 115, and 191 mU) than in the Fast glucose clearance animals (45, 82, and 112 mU). Flow rates between the pools were not significantly different. A euglycemic clamp experiment was performed at two insulin infusion rates, each for 4 hr. A significantly higher glucose infusion rate was required to maintain blood glucose at basal levels in the Slow (3 and 9 mg of glucose/kg liveweight [lwt]0.75 per min) than in the Fast glucose clearance animals (1 and 5 mg/kg lwt0.75 per min). The increase in glucose infusion rate when the insulin infusion rate was increased from 0.63 to 3.46 mU/kg lwt0.75 per min (insulin sensitivity index) was significantly greater in Slow than in Fast glucose clearance animals (0.68 vs. 0.35 mU of insulin/kg lwt0.75 per min). There was no difference between the lines in insulin binding to membranes isolated from muscle or adipose tissue. It is concluded that selection for Slow or Fast glucose clearance has altered several aspects of insulin status, but further work is required to identify the primary difference between the lines.