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Am J Physiol Endocrinol Metab 293: E697-E704, 2007. First published June 19, 2007; doi:10.1152/ajpendo.00219.2007
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Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions

Carlotta Gauna,1 Rosalie M. Kiewiet,1 Joop A. M. J. L. Janssen,1 Bedette van de Zande,1 Patric J. D. Delhanty,1 Ezio Ghigo,2 Leo J. Hofland,1 Axel P. N. Themmen,1 and Aart Jan van der Lely1,3

1Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy; 3Postgraduate School of Molecular Medicine, Rotterdam, The Netherlands

Submitted 9 April 2007 ; accepted in final form 18 June 2007

Acylated and unacylated ghrelin (AG and UAG) are gut hormones that exert pleiotropic actions, including regulation of insulin secretion and glucose metabolism. In this study, we investigated whether AG and UAG differentially regulate portal and systemic insulin levels after a glucose load. We studied the effects of the administration of AG (30 nmol/kg), UAG (3 and 30 nmol/kg), the ghrelin receptor antagonist [D-Lys3]GHRP-6 (1 µmol/kg), or various combinations of these compounds on portal and systemic levels of glucose and insulin after an intravenous glucose tolerance test (IVGTT, D-glucose 1 g/kg) in anesthetized fasted Wistar rats. UAG administration potently and dose-dependently enhanced the rise of insulin concentration induced by IVGTT in the portal and, to a lesser extent, the systemic circulation. This UAG-induced effect was completely blocked by the coadministration of exogenous AG at equimolar concentrations. Similarly to UAG, [D-Lys3]GHRP-6, alone or in combination with AG and UAG, strongly enhanced the portal insulin response to IVGTT, whereas exogenous AG alone did not exert any further effect. Our data demonstrate that, in glucose-stimulated conditions, exogenous UAG acts as a potent insulin secretagogue, whereas endogenous AG exerts a maximal tonic inhibition on glucose-induced insulin release.

acylated ghrelin; insulin secretion; portal vein; rat


Address for reprint requests and other correspondence: C. Gauna, Div. of Endocrinology, Dept. of Internal Medicine, Rm. Ee542, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands (e-mail: c.gauna{at}erasmus.nl)




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