Characterization of the insulin-antagonistic effect of growth hormone in man

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Abstract
The insulin-antagonistic effect of growth hormone was characterized by infusing the hormone at three different infusion rates (6, 12 or 24 mU·kg−1·min−1) for one h in 11 healthy subjects. The insulin effect was measured with the euglycaemic clamp technique combined with D-(3-3H)-glucose infusion to evaluate glucose production and utilization. A control study with NaCl (154 mmol·l−1) infusion was also performed. The insulin levels during the clamps were similar in all studies (36±0.2 mU·l−1). Peak growth hormone levels were reached at 60 min (growth hormone 6mU·kg−1·h−1: 31±5; growth hormone 12 mU·kg−1·h−1: 52±4 and growth hormone 24 mU·kg−1·h−1: 102±8mU·l−1). The insulin-antagonistic effect of growth hormone started after ∼2 h, was maximal after 4–5 h (∼39% inhibition of glucose infusion rate between control and growth hormone 24 mU·kg−1·h−1) and lasted for 6–7 h after peak levels. The resistance was due to a less pronounced insulin effect both to inhibit glucose production and to stimulate glucose utilization. Growth hormone infusion of 12 mU·kg−1·h−1 induced a similar insulin-antagonistic effect as the higher infusion rate whereas 6 mU·kg−1·h−1 induced a smaller response with a duration of 1 h between 3–4 h after peak levels of growth hormone. The present study demonstrates that growth hormone levels similar to those frequently seen in Type 1 (insulin-dependent) diabetic patients during poor metabolic control or hypoglycaemia, have pronounced insulin-antagonistic effects. The effects starts after about 2–3 h, is maximal after 4–5 h and lasts for about 6–7 h. Both duration and inhibitory effect of growth hormone are related to the plasma levels, where a maximal effect is seen at about 50 mU·l−1 or higher.