Glucocorticoids suppress insulin secretion, inhibit glucose uptake in peripheral tissues, and promote gluconeogenesis in the liver. These effects are known to be mediated via genomic mechanisms of slow onset. Despite recent evidence on rapid non-genomic glucocorticoid signaling in several organs, there is no information on rapid glucocorticoid effects on carbohydrate metabolism in humans.
Here we present data on the rapid effects of hydrocortisone on the metabolic response in a frequently sampled intravenous glucose tolerance test (FSIGT). Ten healthy men were recruited in a randomized placebo-controlled cross-over study. They received intravenously a bolus of placebo/0.6 mg/kg hydrocortisone and 4 min afterwards 330 mg/kg glucose. During the following 180 min, blood samples were taken for the measurement of glucose, insulin and C-peptide. Minimal model analysis was performed for the calculation of beta cell function, hepatic insulin extraction and insulin sensitivity.
Hydrocortisone attenuated the rise in plasma glucose following glucose administration during the first 2 h of the study (P=0.017), but led to higher plasma glucose concentrations during the last hour (P=0.004). Hydrocortisone increased the first phase insulin secretion (P=0.003) and decreased the late phase insulin secretion (P=0.03). Minimal model analysis revealed that hydrocortisone reduced the total hepatic extraction of insulin (P=0.009) without significantly changing insulin sensitivity.
In summary, we present here evidence that the administration of glucocorticoids a few minutes before an intravenous glucose load induces non-classical changes in beta cell function and hepatic insulin clearance, but does not modulate insulin sensitivity during the FSIGT.
25 - 29 Apr 2009
European Society of Endocrinology