The effect of propylthiouracyl-induced low thyroid function on secretion response and action of insulin in sheep

The effect of propylthiouracyl (PTU)-induced low thyroid function on insulin responsiveness to glucose and glucose responsiveness to insulin in sheep was studied by performing hyperglycemic and euglycemic clamp experiments. All sheep were maintained at a level of 125% daily metabolizable energy intake and were housed in an environmental room that was maintained at 20 degrees C with a 16-hr lighting period. In the first study, eight female Suffolk sheep were divided equally into two groups and were subjected to oral PTU treatments of 4 mg/kg body weight (BW) per day for 7 d (low PTU) and 8 mg/kg BW per day for 14 d (high PTU). A hyperglycemic clamp experiment was conducted in each group on both control and PTU treatment periods. Plasma concentrations of triiodothyronine and thyroxine decreased (P < 0.05) in high PTU-treated sheep compared with those of low PTU-treated and control sheep. Both PTU treatments did not significantly influence basal insulin and glucose levels. Results of the hyperglycemic clamp experiment indicated that the mean plasma insulin increment and the ratio of mean plasma insulin increment to glucose infusion rate were significantly higher (P < 0.01) in high PTU-treated sheep than in low PTU-treated and control sheep. In the second study, the PTU treatment (8 mg/kg BW per day) was applied for 17 d in four male Suffolk sheep. A euglycemic clamp experiment with two insulin infusion rates (1.0 and 10.0 mU/kg per minutes) for two sequential periods of 2 hr each and thyroid hormone responses to intrajugular injection of thyrotropin-releasing hormone (1 microgram/kg BW) were performed in each sheep on both control and PTU treatment periods. In the euglycemic clamp experiment, the glucose infusion rate and the ratio of glucose infusion rate to mean plasma insulin increment were significantly reduced (P < 0.05) during the PTU treatment period for 10.0 mU/kg BW per minute of insulin infusion rate. The response areas of plasma thyroxine and triiodothyronine to thyrotropin-releasing hormone injection were blunted (P < 0.01) in PTU-treated sheep compared with those of control sheep. The high PTU treatment induced low thyroid function, enhanced insulin secretion response, and impaired insulin action in sheep.