Endocrine Abstracts (2008) 16 P541

Glucagon suppression of total but not of acylated ghrelin is preserved in obesity: the impact on appetite control

Ayman M Arafat1, Aikaterini Adamidou1, Bärbel Otto2, Martin O Weickert1, Frank H Perschel3, Joachim Spranger1, Christof Schöfl4, Matthias Möhlig1 & Andreas F H Pfeiffer1


1Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany; 2Medical Department- Innenstadt, University Hospital Munich, Munich, Germany; 3Department of Clinical Chemistry and Pathobiochemistry, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany; 4Division of Neuroendocrinology, Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.


Objective: The mechanisms underlying the well known glucagon-induced satiety effect are unclear. As we showed recently, the glucagon-induced reduction in total ghrelin, that might be responsible for this effect, is exerted at hypothalamus–pituitary level. The aim of the present study was to further evaluate glucagon’s suppressive effect on both total and acylated-ghrelin in obesity with respect to its role in appetite control.

Methods: Prospectively, we studied the endocrine and metabolic responses to intramuscular glucagon administration in 14 lean (6 males; BMI 21.6±0.6 kg/m2) and 12 obese healthy subjects (6 males; BMI 33.9±1.6 kg/m2). All subjects were proved to have an intact pituitary function.

Results: Age, fasting glucose, glucagon and acylated-ghrelin concentrations were comparable between both groups. Fasting insulin was significantly higher and baseline total-ghrelin was significantly lower in obese than in lean subjects. Total-ghrelin significantly decreased after glucagon administration in both obese (mean±S.E.M.: 706±54 vs 618±47 pg/ml, P<0.01) and lean subjects (1181±133 vs 1023±102, P<0.01). Acylated-ghrelin did not change significantly in obese, whereas a significant decrease occurred in lean subjects (306±58 vs 209±43 pg/ml, P<0.05). However, hunger scores significantly decreased in both groups: lean (3.2±0.3 vs 2.3±0.2, P<0.05) and obese subjects (4.1±0.5 vs 2.9±0.4, P<0.05).

Conclusions: We show that glucagon significantly decreases total- and acylated-ghrelin in lean healthy subjects but fails to affect acylated-ghrelin in obese individuals. The glucagon-induced satiety effect remained intact indicating the role of changes in total rather than in acylated-ghrelin in mediating this effect.