CHARACTERIZATION OF THE INSULIN ANTAGONISTIC EFFECT OF GROWTH-HORMONEIN INSULIN-DEPENDENT DIABETES-MELLITUS

To characterize its insulin-antagonistic effect, growth hormone (GH) w as infused at variable rates (24, 12 or 6 mU kg(-1) min(-1)) for 1 h i n 7 IDDM patients. Saline infusion was used as control (C) and all pat ients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d-(3-H-3)-g lucose to evaluate glucose turnover. The insulin levels during the cla mps were similar in all studies (23 +/- 3 mU l(-1)). The infusions pro duced peak GH levels of (24 rate 24) 157 +/- 11, (12 rate = 12) 76 +/- 7, and (6 rate = 6) 45 +/- 8 mU 1(-1) (mean +/- SEM). The insulin-ant agonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 +/- 0.4 mg kg(-1) min(- 1), p < 0.01). The resistance was due to a less pronounced effect of i nsulin to both inhibit rate of appearance and to stimulate rate of dis appearance. Infusion of GH at 12 mU kg(-1) min(-1) induced a less pron ounced insulin resistance both with regards to maximal effect (glucose infusion rate C - GH 1.4 +/- 0.5 mg kg(-1) min(-1), p < 0.05) and dur ation (3 h). At 6 mU kg(-1) min(-1), a clear GH-induced insulin-antago nistic effect was only seen during the third hour of the clamp (glucos e infusion rate C-GH 1.3 +/- 0.5 mg kg(-1) min(-1), p < 0.05). GH infu sion impaired the effect of insulin to lower both the levels of free f atty acids (NEFA) and glycerol between 2 and 5 h after the start of th e infusion (NEFA, C:110 +/- 29, 24:303 +/- 95, p < 0.05: glycerol, C:3 2 +/- 4, 24:50 +/- 7 mu mol l(-1), p < 0.05). The present study theref ore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and respons e. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.