Ghrelin is a potent growth hormone (GH) secretagogue in rats and in humans. Since stomach is the main source of circulating ghrelin, gastrectomy reduces plasma ghrelin concentrations by 65%. The implications of decreased circulating ghrelin on GH secretion have not yet been investigated. Furthermore, the neuroendocrine pathways through which ghrelin acts to release GH are largely unknown. We aimed to investigate GH response after insulin induced hypoglycemia (ITT) and after systematically administered ghrelin in gastrectomized patients. Ten patients (BMI 22.8 plus/minus SD 0.8 kilograms per meter(super)2(/super)) who underwent gasterctomy for various reasons were included in the study. Twelve healthy normal weight subjects (BMI 22.6 plus/minus SD 0.8 kilograms per meter(super)2 (/super)) were also studied. At baseline circulating ghrelin and IGF-1 levels were determined and GH and ghrelin concentrations were also measured during ITT. Ghrelin was administered 1 micro gram per kilogram of body weight i.v. Circulating ghrelin and IGF-1 levels in gastrectomized patients were decreased compared to healthy subjects, respectively (total ghrelin -Lynco; 1204.1 plus/minus SD 56.4 vs 2296 plus/minus SD 200.9 picograms per mililiter, p<0.05). IGF-1 was 10.3 plus/minus SD 1.7 nanomols per liter (range 11-35 nanomols per liter). Despite low ghrelin levels, GH response after insulin induced hypoglycemia reached a mean peak of 26.6 plus/minus SD 3.8 micrograms per liter (GH Delfia Wallac). Circulating plasma ghrelin levels were not modified during insulin induced hypoglycemia. Peripherally administered ghrelin caused more potent GH release in gasterectomized patients 68.0 plus/minus SD 10.0 micrograms per liter then in healthy subjects 40.7 plus/minus SD 6.1 micrograms per liter p<0.005.
Gastrectomized patients are in a steady 'low ghrelin ' state. These patients are very sensitive to exogenous ghrelin. They also display potent GH responses to ITT. Factors responsible for low IGF-1 are other than GH. Circulating ghrelin levels are not modified during ITT. Circulating ghrelin does not mediate GH response to insulin induced hypoglycemia
01 - 03 Nov 2004
Society for Endocrinology