THE INSULIN STATUS OF SHEEP WITH GENETIC-DIFFERENCES IN GLUCOSE CLEARANCE

Lines of sheep have been selected for Slow or Fast glucose clearance a fter a glucose tolerance test. The aim of this work was to establish w hat 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 concentr ation were studied in three different experiments. After the injection of [I-125]insulin, blood was sampled for 300 min. The change in radio activity with time was used in a three-compartment series model to est imate 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 [1wt](0.75) per min) than in the Fast g lucose clearance animals (1 and 5 mg/kg 1wt(0.75) per min). The increa se in glucose infusion rate when the insulin infusion rate was increas ed from 0.63 to 3.46 mU/kg 1wt(0.75) per min (insulin sensitivity inde x) was significantly greater in Slow than in Fast glucose clearance an imals (0.68 vs. 0.35 mU of insulin/kg 1wt(0.75) 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 Slo w or Fast glucose clearance has altered several aspects of insulin sta tus, but further work is required to identify the primary difference b etween the lines.