CHARACTERIZATION OF THE INSULIN ANTAGONISTIC EFFECT OF GROWTH-HORMONE IN INSULIN-DEPENDENT DIABETES-MELLITUS

To characterize its insulin-antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 mU kg(-1) min(-1)) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d-(3-H-3)-glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 +/- 3 mU l(-1)). The infusions produced 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-antagonistic 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 insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg(-1) min(-1) induced a less pronounced 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 duration (3 h). At 6 mU kg(-1) min(-1), a clear GH-induced insulin-antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C-GH 1.3 +/- 0.5 mg kg(-1) min(-1), p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 +/- 29, 24:303 +/- 95, p < 0.05: glycerol, C:32 +/- 4, 24:50 +/- 7 mu mol l(-1), p < 0.05). The present study therefore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.