Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man

Aims: This study was undertaken to determine the effects of a short-term de xamethasone treatment on hepatic sensitivities to insulin and glucagon. Methods: Eleven healthy subjects were studied during one or several of four protocols. In all protocols, somatostatin was infused continuously to inhi bit pancreatic hormone secretion. In protocol 1, basal insulin was infused over 300 min while glucagon was infused at a rate of 0.5 mg/kg(-1)/min(-1) during 180 min, then at a rate of 1.5 ng/kg(-1)/min(-1) during 150 min. In protocol 2, the same experiment was performed after a 2 day treatment with 8 mg/day dexamethasone. In protocol 3, the two-step glucagon infusion was p erformed during insulin infusion at a rate aimed to reproduce the hyperinsu linemia observed during protocol 2. In protocol 4, continuous basal insulin and low glucagon (0.5 mg/kg(-1)/min(-1)) were infused over 330 min. Results: In protocol 1, plasma glucose rose transiently by 2.0 +/- 0.3 mmol /l when the glucagon rate was increased and glucose production increased by 1.4 +/- 0.5 mu mol/kg(-1)/min(-1). In protocol 2, the insulin infusion rat e (1.85 +/- 0.36 nmol/kg(-1)/min(-1)) required to maintain glycemia was 3.3 -fold higher than during protocol 1. Glucagon-induced stimulation of glycem ia (by 1.47 +/- 0.5 mmol/l) and endogenous glucose production (by 0.8 +/- 0 .3 mu mol/kg(-1)/min(-1)) were blunted, but not abolished. In protocol 3, e ndogenous glucose production was suppressed by 75% by hyperinsulinemia and was not stimulated when the glucagon infusion rate was increased. In protoc ol 4, endogenous glucose production did not change significantly with time. Conclusion: These results indicate that high dose glucocorticoids induce a marked hepatic insulin resistance. Stimulation of glucose production by hyp erglucagonemia was maintained in spite of hyperinsulinemia which can be att ributed to either hepatic insulin resistance and/or increased hepatic gluca gon sensitivity. (C) 2000 Harcourt Publishers Ltd.