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Endocrinology Vol. 144, No. 3 916-921
Copyright © 2003 by The Endocrine Society

ARTICLE

Dose-Dependent Inhibition by Ghrelin of Insulin Secretion in the Mouse

Martina Kvist Reimer, Giovanni Pacini and Bo Ahrén

Department of Medicine (M.K.R., B.A.), Lund University, Lund 22184, Sweden; and Institute of Biomedical Engineering (Istituto di Ingeneria Biomedica-Consiglio Nazionale delle Ricerche) (G.P.), Padua I-35127, Italy

Address all correspondence and requests for reprints to: Dr. Bo Ahrén, Department of Medicine, Biomedical Center B11, Lund University, Lund 22184, Sweden. E-mail: Bo.Ahren{at}med.lu.se.

Ghrelin is produced by stomach oxyntic cells and thought to be involved in the regulation of body weight and food intake. We demonstrate here that the peptide inhibits insulin secretion from overnight-incubated mouse islets in the presence of 8.3, 11.1, and 22.2 mmol/liter glucose. Ghrelin was most efficient at 1 nmol/liter and its effect disappeared by raising the dose more than 25 nmol/liter. Also, insulin secretion in the presence of high K+ concentrations (20 mmol/liter) was inhibited by ghrelin. Furthermore, when administered iv to mice together with glucose (1 g/kg), ghrelin (50 nmol/kg) inhibited both the rapid 1-min insulin response (364 ± 90 vs. 985 ± 114 pmol/liter in controls, P < 0.001) and the area under the 50 min curve of insulin concentration (12.6 ± 1.2 vs. 15.6 ± 1.2 nmol/liter x 50 min; P = 0.046) without affecting the glucose disposal rate, insulin sensitivity or glucose effectiveness, i.e. glucose disposal independent from any dynamic change in insulin. The insulinostatic effect of ghrelin was inversely related to insulin sensitivity. In contrast, ghrelin had no influence at the lower dose of 5 nmol/kg and only slightly inhibited insulin secretion at the higher dose of 150 nmol/kg. These findings therefore show that ghrelin inhibits glucose-stimulated insulin secretion in the mouse. The effect is dependent on the dose and elicited on distal signaling steps in islet cells. The results suggest that the islet ß-cells are targets for ghrelin.




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