Metabolomic linkage reveals functional interaction between glucose-dependent insulinotropic polypeptide and ghrelin in humans.

Metabolomic linkage reveals functional interaction between glucose-dependent insulinotropic polypeptide and ghrelin in humans.
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代谢组学联系揭示了人类葡萄糖依赖性促胰岛素多肽和生长素释放肽之间的功能相互作用

DOI:
10.1152/ajpendo.00154.2011
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发表时间:
2011
期刊:
American journal of physiology. Endocrinology and metabolism
影响因子:
--
通讯作者:
Pfeiffer AF
Pfeiffer AF
中科院分区:
--
文献类型:
--
作者:
Rudovich NN;Nikiforova VJ;Otto B;Pivovarova O;Gögebakan O;Erban A;Möhlig M;Weickert MO;Spranger J;Tschöp MH;Willmitzer L;Nauck M;Pfeiffer AF

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胃肽生长素释放肽促进能量储存、食欲和食物摄入。营养摄入通过可能涉及胰岛素和胃肠激素的分子机制强烈抑制循环中的生长素释放肽。越来越多的证据表明葡萄糖依赖性促胰岛素多肽 (GIP) 参与燃料代谢的控制,我们假设 GIP 和/或胰岛素可能直接或通过血浆代谢物的变化影响循环的生长素释放肽。 14 名肥胖受试者在正常血糖高胰岛素钳夹 (EC) 或高血糖高胰岛素钳夹 (HC) 期间在禁食状态下输注 GIP (2.0 pmol·kg−1·min−1) 或安慰剂。除了分析血浆生长素释放肽和胰岛素水平外,还应用 GC-TOF/MS 分析为每个实验创建激素代谢物网络。在这些网络的框架内分析了 GIP 和胰岛素对循环胃饥饿素的影响。在 HC 中,在不存在 GIP 的情况下(相对于基线为 19.2%,P= 0.028)以及存在 GIP 的情况下(33.8%,P= 0.018),ghrelin 水平均下降。尽管胰岛素水平没有显着差异,但在使用 GIP 的 HC 期间,胃饥饿素水平显着低于安慰剂组。在结合 GIP 输注、EC+GIP 和 HC+GIP 实验数据的 GIP 网络中,生长素释放肽通过与一组长链脂肪酸的连接被整合到激素代谢物网络中。相比之下,ghrelin 被排除在没有 GIP 的实验网络之外。 GIP 减少了循环胃饥饿素,并可能通过改变长链脂肪酸库影响了胃饥饿素系统。这些观察结果独立于胰岛素,并为 GIP 参与能量代谢的系统控制提供了潜在的机制基础。
The gastric peptide ghrelin promotes energy storage, appetite, and food intake. Nutrient intake strongly suppresses circulating ghrelin via molecular mechanisms possibly involving insulin and gastrointestinal hormones. On the basis of the growing evidence that glucose-dependent insulinotropic polypeptide (GIP) is involved in the control of fuel metabolism, we hypothesized that GIP and/or insulin, directly or via changes in plasma metabolites, might affect circulating ghrelin. Fourteen obese subjects were infused with GIP (2.0 pmol·kg−1·min−1) or placebo in the fasting state during either euglycemic hyperinsulinemic (EC) or hyperglycemic hyperinsulinemic clamps (HC). Apart from analysis of plasma ghrelin and insulin levels, GC-TOF/MS analysis was applied to create a hormone-metabolite network for each experiment. The GIP and insulin effects on circulating ghrelin were analyzed within the framework of those networks. In the HC, ghrelin levels decreased in the absence (19.2% vs. baseline,P= 0.028) as well as in the presence of GIP (33.8%,P= 0.018). Ghrelin levels were significantly lower during HC with GIP than with placebo, despite insulin levels not differing significantly. In the GIP network combining data on GIP-infusion, EC+GIP and HC+GIP experiments, ghrelin was integrated into hormone-metabolite networks through a connection to a group of long-chain fatty acids. In contrast, ghrelin was excluded from the network of experiments without GIP. GIP decreased circulating ghrelin and might have affected the ghrelin system via modification of long-chain fatty acid pools. These observations were independent of insulin and offer potential mechanistic underpinnings for the involvement of GIP in systemic control of energy metabolism.
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