ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 11 P642

Glucagon-induced suppression of ghrelin secretion is exerted at hypothalamus-pituitary level and is not mediated by an increase in catecholamine secretion

MA Arafat1, F Perschel3, B Otto2, M Weickert1, H Rochlitz1, C Schöfl1, J Spranger1, M Möhlig1 & AFH Pfeiffer1

1Department of Endocrinology, Diabetes and Nutrition, Charité-University-Medicine Berlin, Campus Benjamin Franklin and Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehb, Berlin, Germany; 2Medical Department- Innenstadt, University Hospital, Munich, Germany; 3Department of Clinical Chemistry and Pathobiochemistry, Benjamin Franklin Medical Center, Charité University, Berlin, Germany.

Objective: The mechanisms underlying the well known glucagon-induced satiety effect are unclear. We showed earlier that glucagon induces a remarkable decrease in the orexigenic hormone: ghrelin. It was the aim of the present study to further evaluate the effect of glucagon on ghrelin secretion and the possible site of origin of this effect.

Methods: We studied the endocrine and metabolic responses to intramuscular glucagon administration in 23 subjects (17 men and 6 women; age 21–68 years; BMI 27.1±1.2 kg/m2) with a known hypothalamic-pituitary lesion and at least one pituitary hormone deficiency and in 23 healthy subjects as controls (15 men and 8 women; age 20–65 years; BMI 25.8±1.1 kg/m2). We also measured catecholamine levels in 14 healthy subjects (7 men) to evaluate their role in mediating the glucagon-induced suppression of ghrelin.

Results: The AUC240-ghrelin significantly decreased in controls (P<0.001) but not in patients (P=0.446). The AUC240-ghrelin was significantly lower in controls when compared to patients [meanAUC240±SEM: 201.5±6.1 vs 233.2±8.8; (P=0.005)]. Changes in glucagon, glucose and insulin levels were comparable between both groups. In healthy subjects no significant changes in noradrenaline or adrenaline levels were observed during the first 240 min. after glucagon administration.

Conclusion: We show that i.m. glucagon significantly decreases ghrelin levels in healthy subjects. However, in the absence of an intact hypothalamic-pituitary axis glucagon failed to decrease ghrelin pointing out to a modulation at the hypothalamic-pituitary level. The mechanisms underlying these effects unlikely include catecholamines, glucose or insulin variations and need to be further elucidated.