title: Serum Insulin Levels Are Reduced by Intravenous Ghrelin Administration but Do Not Correlate with Alcohol Craving in Alcohol-Dependent Individuals.
abstract: BACKGROUND
  Increasing evidence supports a role for appetite-regulating pathways like ghrelin, insulin, and leptin in alcoholism. We previously reported that intravenous (i.v.) exogenous ghrelin increases alcohol craving. We also reported i.v. ghrelin reduces endogenous serum leptin, whose levels, in turn, negatively correlated with alcohol craving. Exogenous ghrelin administration decreases insulin secretion both in vitro and in vivo experiments. This study tested the hypothesis that i.v. ghrelin may also decrease endogenous serum insulin levels in alcoholic individuals. Additionally, we explored possible correlations between serum insulin and alcohol craving, since a correlation between insulin and alcohol craving was previously reported.
  
  
  METHODS
  This was a double-blind, placebo-controlled human laboratory study ( n =43). Non-treatment-seeking, alcohol-dependent, heavy drinkers were randomized to receive i.v. ghrelin or placebo, followed by an alcohol cue-reactivity procedure.
  
  
  RESULTS
  There was a main effect for i.v. ghrelin, compared to placebo in reducing serum insulin ( P <.05). There was also a time effect ( P <.001) but not ghrelin x time interaction ( P >.05). We did not find a correlation between the reduction of serum insulin and alcohol craving ( P >.05). The change in serum insulin was consistent with a parallel reduction in serum connective-peptide in the ghrelin group compared with placebo, although this difference did not reach statistical significance ( P =.076). No similar effects were found for other glucose-regulating hormones analyzed i.e. glucagon, glucagon-like peptide-1, and gastric inhibitory peptide ( P s>.05).
  
  
  CONCLUSIONS
  These findings indicate i.v. ghrelin administration has an effect on reducing serum insulin in alcohol-dependent individuals; however, the reduction of insulin did not correlate with changes in alcohol cue-elicited craving. We speculate that, unlike for leptin, the interactions between ghrelin and insulin relationship are limited at the peripheral level. However, mechanistic studies are needed to investigate this hypothesis.
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Haass-Koffler
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Giovenco
authors.forename: Mary R
authors.initials: MR
authors.lastname: Lee
authors.forename: William H
authors.initials: WH
authors.lastname: Zywiak
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: de la Monte
authors.forename: George A
authors.initials: GA
authors.lastname: Kenna
authors.forename: Robert M
authors.initials: RM
authors.lastname: Swift
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leggio
keywords: alcohol craving; alcoholism; ghrelin; glucagon; incretins; insulin; leptin