Haass-Koffler Carolina L, Giovenco Danielle E, Lee Mary R, Zywiak William H, de la Monte Suzanne M, Kenna George A, Swift Robert M, Leggio Lorenzo
Int J Neuropsychopharmacol. 2016 May 10;19(10):pyw048. doi: 10.1093/ijnp/pyw048.
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.
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.
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).
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.
越来越多的证据支持食欲调节途径如胃饥饿素、胰岛素和瘦素在酒精中毒中发挥作用。我们之前报道静脉注射外源性胃饥饿素会增加对酒精的渴望。我们还报道静脉注射胃饥饿素会降低内源性血清瘦素水平，而瘦素水平又与对酒精的渴望呈负相关。在体外和体内实验中，外源性胃饥饿素给药均会减少胰岛素分泌。本研究检验了静脉注射胃饥饿素可能也会降低酒精依赖个体内源性血清胰岛素水平这一假设。此外，由于之前报道过胰岛素与对酒精的渴望之间存在相关性，我们探究了血清胰岛素与对酒精的渴望之间可能存在的相关性。
这是一项双盲、安慰剂对照的人体实验室研究（n = 43）。未寻求治疗的酒精依赖重度饮酒者被随机分为接受静脉注射胃饥饿素或安慰剂组，随后进行酒精线索反应程序。
与安慰剂相比，静脉注射胃饥饿素在降低血清胰岛素方面有主要效应（P <.05）。也存在时间效应（P <.001），但胃饥饿素×时间交互作用不显著（P >.05）。我们未发现血清胰岛素降低与对酒精的渴望之间存在相关性（P >.05）。与安慰剂相比，胃饥饿素组血清胰岛素的变化与血清连接肽的平行降低一致，尽管这种差异未达到统计学显著性（P =.076）。对于所分析的其他血糖调节激素，即胰高血糖素、胰高血糖素样肽 - 1和胃抑制肽，未发现类似效应（P值>.05）。
这些发现表明静脉注射胃饥饿素对降低酒精依赖个体的血清胰岛素有作用；然而，胰岛素的降低与酒精线索诱发的渴望变化无关。我们推测，与瘦素不同，胃饥饿素与胰岛素关系之间的相互作用在外周水平上是有限的。然而，需要进行机制研究来探究这一假设。
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