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This Article Full Text Full Text (PDF) All Versions of this Article: EJE-09-0339v1 161/4/567    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Kiewiet, R. M Articles by van der Lely, A. J. PubMed PubMed Citation Articles by Kiewiet, R. M Articles by van der Lely, A. J.

Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes

Division of Endocrinology, Department of Internal Medicine, Erasmus University Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Molinette Hospital, Corso Dogliotti 14, 10126, Turin, Italy² Alize Pharma SAS, 15, chemin du Saquin, 69130 ECULLY, France

(Correspondence should be addressed to R M Kiewiet; Email: r.kiewiet{at}erasmusmc.nl)

Objective: To investigate the effects of unacylated ghrelin (UAG) and co-administration of acylated ghrelin (AG) and UAG in morbid obesity, a condition characterized by insulin resistance and low GH levels.

Design and method: Eight morbidly obese non-diabetic subjects were treated with either UAG 200 µg, UAG 100 µg in combination with AG 100 µg (Comb) or placebo in three episodes of 4 consecutive days in a double-blind randomized crossover design. Study medication was administered as daily single i.v. bolus injections at 0900 h after an overnight fast. At 1000 h, a standardized meal was served. Glucose, insulin, GH, free fatty acids (FFA) and ghrelin were measured up to 4 h after administration.

Results: Insulin concentrations significantly decreased after acute administration of Comb only, reaching a minimum at 20 min: 58.2±3.9% of baseline versus 88.7±7.2 and 92.7±2.6% after administration of placebo and UAG respectively (P<0.01). After 1 h, insulin concentration had returned to baseline. Glucose concentrations did not change after Comb. However, UAG administration alone did not change glucose, insulin, FFA or GH levels.

Conclusion: Co-administration of AG and UAG as a single i.v. bolus injection causes a significant decrease in insulin concentration in non-diabetic subjects suffering from morbid obesity. Since glucose concentration did not change in the first hour after Comb administration, our data suggest a strong improvement in insulin sensitivity. These findings warrant studies in which UAG with or without AG is administered for a longer period of time. Administration of a single bolus injection of UAG did not influence glucose and insulin metabolism.

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