title: Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes.
abstract: 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Molinette Hospital, Corso Dogliotti 14, 10126, Turin, Italy. r.kiewiet@erasmusmc.nl
authors.forename: Rosalie M
authors.initials: RM
authors.lastname: Kiewiet
authors.forename: Maarten O
authors.initials: MO
authors.lastname: van Aken
authors.forename: Kim
authors.initials: K
authors.lastname: van der Weerd
authors.forename: Piet
authors.initials: P
authors.lastname: Uitterlinden
authors.forename: Axel P N
authors.initials: AP
authors.lastname: Themmen
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: Patric J D
authors.initials: PJ
authors.lastname: Delhanty
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Thierry
authors.initials: T
authors.lastname: Abribat
authors.forename: Aart Jan
authors.initials: AJ
authors.lastname: van der Lely
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin