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

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 mu g. UAG 100 mu g in combination with AG 100 mu g (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 +/- 3.91% of baseline versus 88.7 +/- 7.2 and 92.7 +/- 2.61% 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.