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Effects of Ghrelin on the Insulin and Glycemic Responses to Glucose, Arginine, or Free Fatty Acids Load in Humans

Division of Endocrinology and Metabolism (F.B., C.Go., A.B., F.P., S.D., M.M., R.D., E.G.), Department of Internal Medicine, University of Turin, 10126 Torino, Italy; and Division of Endocrinology (F.B., C.Ga., A.J.v.d.L.), Department of Internal Medicine, Erasmus University of Rotterdam, 3015 Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: E. Ghigo, M.D., Division of Endocrinology and Metabolism Department of Internal Medicine, University of Turin Corso Dogliotti 14, 10126 Torino, Italy. E-mail: ezio.ghigo{at}unito.it.

Ghrelin possesses central and peripheral endocrine actions including influence on the endocrine pancreatic function. To clarify this latter ghrelin action, in seven normal young subjects [age (mean ± SEM), 28.3 ± 3.1 yr; body mass index, 21.9 ± 0.9 kg/m²), we studied insulin and glucose levels after acute ghrelin administration (1.0 µg/kg iv) alone or combined with glucose [oral glucose tolerance test (OGTT), 100 g orally], arginine (ARG, 0.5 g/kg iv) or free fatty acid (FFA, Intralipid 10%, 250 ml). Ghrelin inhibited (P < 0.05) insulin and increased (P < 0.05) glucose levels. OGTT increased (P < 0.01) glucose and insulin levels. FFA increased (P < 0.05) glucose but did not modify insulin levels. ARG increased (P < 0.05) both insulin and glucose levels. Ghrelin did not modify both glucose and insulin responses to OGTT as well as the FFA-induced increase in glucose levels; however, ghrelin administration was followed by transient insulin decrease also during FFA. Ghrelin blunted (P < 0.05) the insulin response to ARG and enhanced (P < 0.05) the ARG-induced increase in glucose levels. In all, ghrelin induces transient decrease of spontaneous insulin secretion and selectively blunts the insulin response to ARG but not to oral glucose load. On the other hand, ghrelin raises basal glucose levels and enhances the hyperglycemic effect of ARG but not that of OGTT. These findings support the hypothesis that ghrelin exerts modulatory action of insulin secretion and glucose metabolism in humans.

The present study was supported by Eureka Project (Peptido 1923), Ministero dell’Università e della Ricerca Scientifica, University of Turin and Fondazione per lo Studio delle Malattie Endocrino.

Abbreviations: ARG, Arginine; FFA, free fatty acid; GHS, GH secretagogues; GHS-R, GHS receptor; OGTT, oral glucose tolerance test.

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