Studies on the insulin-antagonistic effect of catecholamines in normal man

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Abstract
The insulin-antagonistic effect of adrenaline was studied in seven healthy subjects with the euglycaemic clamp technique using two insulin infusion rates (40 and 1200 mU (m2)−1 min−1). The adrenergic receptor mediating the adrenaline effect was characterized by concomitant infusion of propranolol β 1+β 2-antagonist) or metoprolol (β 1-antagonist). Each subject was studied four times (placebo, adrenaline, adrenaline + propranolol, adrenaline + metoprolol). Glucose turnover was measured with D(3-3H)-glucose. Similar plasma insulin levels were reached in all studies with the two insulin infusion rates (mean; placebo 51 ± 3 and 7421 ± 337 mU/l respectively). Glucose production was completely inhibited by the low insulin level during placebo infusion. Adrenaline antagonized this effect so that a significant glucose production was seen at the low but not at the high insulin level. Propranolol, but not metoprolol, reversed this insulin-antagonistic effeet of adrenaline. Glucose utilization increased from 2.53 ±0.17 to 7.28 ± 0.88 mg · kg−1 · min−1 during placebo when the insulin levels were increased from 4± 0.3 to 51 ± 3 mU/l. Increasing the insulin levels 150-fold to ∼7500 mU/l only doubled the glucose utilization (14.68 ±1.14 mg·kg−1·min−1). Adrenaline induced a pronounced inhibition of glucose utilization at both insulin levels (78% and 37% inhibition respectively). Propranolol, but not metoprolol, prevented this effect of adrenaline. Thus, physiological adrenaline levels exert a pronounced insulin-antagonistic effect which is mediated by β 2-receptor stimulation. The inhibitory effect on glucose uptake is maintained even at high insulin levels when hepatic glucose production is completely abolished.