Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans.

AIMS/HYPOTHESIS: This study examined whether autonomic mechanisms contribute to adaptively increased insulin secretion in insulin-resistant humans, as has been proposed from studies in animals.
METHODS: Insulin secretion was evaluated before and after induction of insulin resistance with or without interruption of neural transmission. Insulin resistance was induced by dexamethasone (15 mg given over 3 days) in nine healthy women (age 67 years, BMI 25.2+/-3.4 kg/m(2), fasting glucose 5.1+/-0.4 mmol/l, fasting insulin 46+/-6 pmol/l). Insulin secretion was evaluated as the insulin response to intravenous arginine (5 g) injected at fasting glucose and after raising glucose to 13 to 15 mmol/l or to >28 mmol/l. Neural transmission across the ganglia was interrupted by infusion of trimethaphan (0.3-0.6 mg kg(-1) min(-1)).
RESULTS: As an indication of insulin resistance, dexamethasone increased fasting insulin (to 75+/-8 pmol/l, p<0.001) without significantly affecting fasting glucose. Arginine-induced insulin secretion was increased by dexamethasone at all glucose levels (by 64+/-12% at fasting glucose, by 80+/-19% at 13-15 mmol glucose and by 43+/-12% at >28 mmol glucose; p <0.001 for all). During dexamethasone-induced insulin resistance, trimethaphan reduced the insulin response to arginine at all three glucose levels. The augmentation of the arginine-induced insulin responses by dexamethasone-induced insulin resistance was reduced by trimethaphan by 48+/-6% at fasting glucose, 61+/-8% at 13-15 mmol/l glucose and 62+/-8% at >28 mmol/l glucose (p<0.001 for all). In contrast, trimethaphan did not affect insulin secretion before dexamethasone was given. CONCLUSIONS/INTERPRETATIONS: Autonomic mechanisms contribute to the adaptative increase in insulin secretion in dexamethasone-induced insulin resistance in healthy participants.