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.


METHODS
Eight morbidly obese non-diabetic subjects were treated with either UAG 200 microg, UAG 100 microg in combination with AG 100 microg (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 + or - 3.9% of baseline versus 88.7 + or - 7.2 and 92.7 + or - 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.


CONCLUSIONS
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.
Kiewiet
Rosalie M
RM
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Molinette Hospital, Corso Dogliotti 14, 10126, Turin, Italy. r.kiewiet@erasmusmc.nl
van Aken
Maarten O
MO
van der Weerd
Kim
K
Uitterlinden
Piet
P
Themmen
Axel P N
AP
Hofland
Leo J
LJ
de Rijke
Yolanda B
YB
Delhanty
Patric J D
PJ
Ghigo
Ezio
E
Abribat
Thierry
T
van der Lely
Aart Jan
AJ
D000215:Acylation; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000097:blood*; D004311:Double-Blind Method; D004338:Drug Combinations; D005215:Fasting / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D054439:Ghrelin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood*; D013618:Tachyphylaxis / Q000502:physiology
D001786:Blood Glucose; D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin