Exp Clin Endocrinol Diabetes 2008; 116 - N8
DOI: 10.1055/s-0028-1096335

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

AM Arafat 1, A Adamidou 1, B Otto 2, MO Weickert 1, FH Perschel 3, J Spranger 1, C Schöfl 1, 4, M Möhlig 1, AFH Pfeiffer 1
  • 1Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin Charité-University Medicine Berlin, Germany and Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
  • 2Medical Department- Innenstadt, University Hospital Munich, Munich, Germany
  • 3Department of Clinical Chemistry and Pathobiochemistry, Campus Benjamin Franklin, Charité-University Medicine Berlin, Germany
  • 4Division of Neuroendocrinology, Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany

Objectives: 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 the 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±0.6kg/m2) and 12 obese healthy subjects (6 males; BMI 33.9±1.6kg/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±SEM: 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). Hunger scores significantly decreased in lean [Satiety index AUC240 : 241.7±18.2 (after glucagon administration) vs. 179.4±11.1 (after placebo administration), p<0.05], but not in obese subjects (231.7±22.6 vs. 278.2±36.9, 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 seems to be related to changes in acylated- rather than in total-ghrelin that are blunted in obese individuals.