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.

Additional Metadata
Keywords adult, article, blood, clinical trial, controlled clinical trial, controlled study, crossover procedure, diabetes mellitus, diet restriction, double blind procedure, drug combination, drug derivative, fatty acid, female, ghrelin, glucose blood level, human, insulin, metabolism, middle aged, morbid obesity, physiology, randomized controlled trial, tachyphylaxis
Persistent URL dx.doi.org/10.1530/EJE-09-0339, hdl.handle.net/1765/17896
Journal European Journal of Endocrinology
Kiewiet-Kemper, R.M, van Aken, M.O, van der Weerd, K, Uitterlinden, P, Themmen, A.P.N, Hofland, L.J, … van der Lely, A-J. (2009). Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes. European Journal of Endocrinology, 161(4), 567–573. doi:10.1530/EJE-09-0339