Division of Endocrinology, Department of Internal Medicine, Erasmus University Medical Centre, CA Rotterdam, The Netherlands.
J Endocrinol Invest. 2011 Jun;34(6):434-8. doi: 10.1007/BF03346709. Epub 2010 Oct 15.
Energy homeostasis and body weight are regulated by a highly complex network involving the brain, the digestive tract, and white adipose tissue (WAT). Knowledge about signaling pathways connecting digestive tract and WAT is limited. Gut hormone ghrelin and adipokine adiponectin are both decreased in obesity and they share a potent effect on insulin sensitivity: both adiponectin and the combination of acylated (AG) and unacylated ghrelin (UAG) improve insulin sensitivity.
In the present study, we evaluated whether acute administration of UAG alone or combined with AG affects adiponectin concentrations.
Eight morbidly obese non-diabetic subjects were treated with either UAG 200 μg, UAG 100 μg + AG 100 μg (Comb), or placebo in 3 episodes in a double blind randomized cross-over design. Study medication was administered as single iv bolus injections at 09:00 h after an overnight fast. High molecular weight (HMW) and total adiponectin, glucose, insulin, and total ghrelin and AG were measured up to 1 h after administration.
HMW and total adiponectin concentrations did not change after administration of either UAG or Comb, nor were they different from placebo. Insulin concentrations decreased significantly after acute administration of Comb, reaching a minimum at 20 min: 58.2 ± 3.9% of baseline.
Acute iv administration of UAG and the combination of UAG and AG in morbidly obese non-diabetic subjects without overt diabetes does not affect total or HMW adiponectin concentrations, neither directly nor indirectly by changing insulin concentrations.
能量平衡和体重由涉及大脑、消化道和白色脂肪组织(WAT)的高度复杂网络调节。关于连接消化道和 WAT 的信号通路的知识有限。胃肠激素 ghrelin 和脂肪因子 adiponectin 在肥胖症中均降低,它们对胰岛素敏感性具有强大的作用:adiponectin 和酰化(AG)和非酰化 ghrelin(UAG)的组合均改善胰岛素敏感性。
在本研究中,我们评估了单独给予 UAG 或与 AG 联合给予是否会影响 adiponectin 浓度。
8 名患有肥胖症的非糖尿病受试者在双盲随机交叉设计的 3 个阶段中分别接受 UAG 200 μg、UAG 100 μg+AG 100 μg(组合)或安慰剂治疗。研究药物在禁食过夜后于 09:00 时作为单次静脉推注给予。在给药后高达 1 小时测量高分子量(HMW)和总 adiponectin、葡萄糖、胰岛素以及总 ghrelin 和 AG。
给予 UAG 或组合后,HMW 和总 adiponectin 浓度均未改变,与安慰剂相比也没有差异。急性给予 Comb 后,胰岛素浓度显著下降,20 分钟时达到最低:基线的 58.2±3.9%。
在没有明显糖尿病的病态肥胖非糖尿病受试者中,静脉内给予 UAG 和 UAG 与 AG 的组合不会影响总 adiponectin 或 HMW adiponectin 浓度,无论是直接还是间接通过改变胰岛素浓度。