Metabolic differences in the effects of insulin on two genetically selected lines of sheep: A dissertation submitted in partial fulfilment of the requirements for the degree of Bachelor of Science with Honours at Lincoln University

Abstract

Glucose tolerance tests were used to select two lines of Coopworth rams. Line 1 animals had high T-Half values and low glucose tolerance while Line 2 animals had low T-Half values and high glucose tolerance. Thus, it was determined from these initial experiments that the Line 2 animals were more capable of removing a load of glucose than the Line 1 animals. Four animals which were extreme in glucose tolerance in each line were further characterised for differences in insulin sensitivity using the euglycaemic clamp experiment. In this investigation, insulin was infused at two levels; 0.6 and 6.0 mU/kglwt/min for 5 and 6 hours respectively, to look at the effect of raising the plasma insulin concentration on glucose utilization by the peripheral tissues. Adipose and muscle biopsies were taken during the clamp experiment to determine if the differences in insulin sensitivity in the periphery between the two lines were occurring in adipose of muscle tissue. From carcass analysis, it was determined that the Line 1 animals were significantly fatter (P<0.01) than the animals in Line 2. The results of the euglycaemic clamp experiment demonstrated that the Line 2 animals had significantly greater (P<0.10) glucose utilization and glucose turnover than the Line 1 animals on increasing the plasma insulin concentration from level 1 to level 2. These results indicated that the Line 2 animals were more sensitive to the hypoglycaemic actions of insulin than the Line 1 animals. It was further demonstrated that on progressing from insulin level 1 to insulin level 2, sheep in Line 2 had a greater increase in glucose turnover relative to the fat content compared to the Line 1 animals. Consistent with this, there was a trend for the Line 2 animals to be more sensitive to the influence of insulin on channelling glucose into fat (as determined by measuring the amount of [U-14C] - glucose incorporated into triglyceride-glycerol. There were no differences between the two lines in insulin stimulation of protein synthesis and hence, it seems reasonable to conclude from the results of this study that the observed differences in carcass composition and insulin sensitivity between animals in the two lines are occurring in the adipose tissue as opposed to the muscle tissue. Since Line 1 which was determined to be the 'fat' line was 'insulin resistant' as compared to Line 2, the 'lean' line, the insulin resistance may be due to a downregulation of insulin receptors or a defect in the insulin receptors of the adipocytes. Defects in the insulin receptors of enlarged adipocytes (for example, in the obese state) have been demonstrated in previous studies.