Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans.
OBJECTIVE
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
Autonomic mechanisms contribute to the adaptative increase in insulin secretion in dexamethasone-induced insulin resistance in healthy participants.
Ahrén
B
B
Department of Clinical Sciences, Lund University, B11 BMC, Sölvegatan 19, 221 84 Lund, Sweden. Bo.Ahren@med.lu.se
D001120:Arginine / Q000378:metabolism; D001341:Autonomic Nervous System / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007700:Kinetics; D008875:Middle Aged; D017698:Postmenopause
D001786:Blood Glucose; D007328:Insulin; D003907:Dexamethasone; D001120:Arginine; D005947:Glucose