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Low Plasma Ghrelin Level in Gastrectomized Patients Is Accompanied by Enhanced Sensitivity to the Ghrelin-Induced Growth Hormone Release

Institute of Endocrinology, Diabetes, and Metabolism (V.P., D.Mil., S.P., M.Dj., M.Do., S.D., D.Mic., G.C.), Institute of Abdominal Surgery (P.P.), University Clinical Center, Belgrade, Laboratory Consilium (J.G.), 11000 Belgrade, Serbia and Montenegro; and Department of Physiology (C.D.) and Complejo Hospitalario, Endocrine Section (F.F.C.), Faculty of Medicine, Santiago de Compostela University, E-15780 Santiago de Compostela, Spain

Address all correspondence and requests for reprints to: Professor Dr. Vera Popovic, M.D., Ph.D., F.R.C.P., Neuroendocrine Unit, Institute of Endocrinology, Diabetes Mellitus and Metabolism, University Clinical Center, Dr Subotic 13, 11000 Belgrade, Serbia. E-mail: popver{at}eunet.yu.

Ghrelin is a brain-gut peptide with potent GH-releasing activities. It has been suggested that the majority of circulating ghrelin originates from the stomach, with a smaller portion from the small intestine. Gastrectomy (GASTRX) significantly reduces circulating ghrelin concentrations. The implication of decreased circulating ghrelin on the somatotropic axis post GASTRX has not been studied. Therefore, we aimed to investigate the somatotropic axis in 10 gastrectomized patients who underwent total GASTRX for various reasons at least 2 yr ago. At baseline circulating total ghrelin, GH, IGF-I, and IGF binding protein (IGFBP)-3 levels were measured. The GH stimulation test consisted of an insulin-induced hypoglycemia, ghrelin in two iv bolus doses (0.1 and 1 µg/kg), and a GHRH test. GH sensitivity was assessed by an IGF-I generation test. All the tests were performed 2 wk apart.

At baseline serum ghrelin levels were reduced by 55% in GASTRX patients, compared with the control group (P < 0.05). IGF-I (P < 0.05) and IGFBP-3 (P < 0.01) levels were also significantly lower than in controls. GH response to the insulin-induced hypoglycemia test in both GASTRX and control subjects was of similar magnitude, whereas circulating plasma ghrelin levels in GASTRX patients were not modified during hypoglycemia. Both doses (0.1 and 1.0 µg/kg) of ghrelin stimulated GH release significantly more in GASTRX than control subjects, respectively (peak mean GH ± SE: 18.2 ± 5.6 vs. 5.4 ± 1.3 µg/liter, P < 0.03; and 58.7 ± 7.5 vs. 35.3 ± 1.9 µg/liter, P < 0.01). There was no difference in GHRH-induced GH response between GASTRX patients and control subjects (P > 0.05). Concomitantly, increased increments in IGF-I and IGFBP-3 to a single bolus of GH were found (P < 0.03). In conclusion, our data suggest that low circulating ghrelin levels, found in GASTRX patients, are accompanied by enhanced ghrelin sensitivity with respect to GH response. This is associated with increased GH responsiveness. GASTRX is a state of acquired chronic hypoghrelinemia that may require replacement with ghrelin, and it is tempting to speculate that this may affect the GH-IGF-IGFBP axis.

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