Plasma levels of active form of ghrelin during oral glucose tolerance test in patients with anorexia nervosa.

Abstract

Ghrelin is an acylated peptide, whose octanoyl modification is essential for its biological activities. Previous studies demonstrated that fasting plasma ghrelin levels were high in anorectic patients, suggesting ghrelin may play an important role in the pathophysiology of anorexia nervosa. However, antibodies used in previous work to measure ghrelin concentrations in human blood do not distinguish between the active form of ghrelin (active ghrelin) and desacyl ghrelin with no biological activities. Therefore, we studied plasma levels of active ghrelin during oral glucose tolerance test (OGTT) in anorectic patients, using a radioimmunoassay (RIA) specific for active ghrelin. Active ghrelin response to OGTT was evaluated in five female anorectic patients and seven age-matched control females. All subjects were given a 75 g/225 ml glucose solution orally after overnight fasting. For RIA of active ghrelin, 1 N hydrogen chloride was added to the samples at final concentration of 0.1 N immediately after separation of plasma. Plasma basal levels of active ghrelin were significantly higher in anorectic patients than in controls (52.1+/-10.5 vs 21.2+/-3.1 fmol/ml, P<0.01). They were significantly decreased during OGTT in anorectic patients and in controls, reaching a nadir of 49.0+/-7.7% and 57.3+/-4.5% of the basal levels, respectively. These results suggest that hyperghrelinemia in anorectic patients is caused at least partly by increased secretion of active ghrelin and that glucose ingestion suppresses active ghrelin release in these patients.