Glucagon suppression of ghrelin secretion is exerted at hypothalamus-pituitary level

Context: The mechanisms underlying the well-known glucagon-induced satiety effect are unclear. Recently, we showed that glucagon induces a remarkable decrease in the orexigenic hormone ghrelin that might be responsible for this effect. Objective: The objective of this study was to evaluate the putative role of the hypothalamic pituitary axis in glucagon's suppressive effect on ghrelin secretion. Design, Subjects, and Methods: Prospectively, we studied the endocrine and metabolic responses to im glucagon administration in 22 patients (16 males; age, 21-68 yr; body mass index, 28.1 +/- 1.1 kg/m(2)) with a known hypothalamic-pituitary lesion and at least one pituitary hormone deficiency. Control experiments were performed in 27 healthy subjects (15 males; age, 19-65 yr; body mass index, 25.5 +/- 0.9 kg/m(2)). Results: The suppression of ghrelin by glucagon measured as area under the curve(240min) was significantly greater in controls when compared with patients (P < 0.01). Although there was a significant decrease in ghrelin in controls (P < 0.001), ghrelin was almost unchanged in patients (P = 0.359). Changes in glucagon, glucose, and insulin levels were comparable between both groups. Conclusions: We show that the hypothalamic-pituitary axis plays an essential role in the suppression of ghrelin induced by im glucagon administration. Glucagon significantly decreases ghrelin levels in healthy subjects. However, in the absence of an intact hypothalamic-pituitary axis, this effect was abolished. The mechanisms responsible for our observation are unlikely to include changes in glucose or insulin levels.