Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy.
Metabolism. 2010 Jul;59(7):988-92. doi: 10.1016/j.metabol.2009.10.021. Epub 2010 Feb 12.
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) potently augment insulin response to glucose. It is less known what their effects are insulin clearance, which also contributes to peripheral hyperinsulinemia observed after administration of incretins together with glucose. The aims of this study were the quantification of C-peptide secretion and the evaluation of insulin clearance after administration of GIP with glucose. This allows the assessment of GIP's effects on hyperinsulinemia. In addition, GIP's effects were compared with those of GLP-1. Anesthetized female NMRI mice were injected intravenously with glucose alone (1 g/kg, n = 35) or glucose together with GIP (50 microg/kg, n = 12). Samples were taken through the following 50 minutes, and C-peptide and insulin concentrations were used to reconstruct C-peptide secretion rate and insulin clearance. In a previous study, GLP-1 (10 microg/kg) was used in 12 mice; and we used those GLP-1 results to compare GIP effects with those of GLP-1. C-peptide secretion rate peaked at 1 minute after glucose injection, and the immediate part of the insulin-releasing process was markedly augmented by both incretin hormones (1-minute suprabasal increment secretory rate was 20 +/- 2 pmol/min for GIP and 28 +/- 2 pmol/min for GLP-1, vs only 9 +/- 1 pmol/min for glucose alone; P < .001). Until 10 minutes after administration, C-peptide secretion remained higher with incretins (P < .0001), whereas starting from 20 minutes, the 3 patterns were undistinguishable (P > .2). Insulin clearance, previously shown to be abridged by 46% with GLP-1, was reduced only by a nonsignificant (P = .27) 21% with GIP. This study thus shows that the 2 incretins markedly augment glucose-stimulated insulin secretion in mice by a preferential action on the immediate response to glucose of insulin secretion. However, the action of GIP is less effective than that of GLP-1. Insulin clearance with GIP is not significantly reduced. We conclude that GIP is less potent than GLP-1 in inducing glucose-stimulated hyperinsulinemia in the mouse.
胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性胰岛素促分泌多肽（GIP）强烈促进葡萄糖刺激胰岛素的反应。人们对它们对胰岛素清除的影响知之甚少，而胰岛素清除也有助于在给予肠促胰岛素和葡萄糖后观察到的外周性高胰岛素血症。本研究的目的是定量测定 GIP 与葡萄糖给药后 C 肽的分泌，并评估胰岛素的清除率。这允许评估 GIP 对高胰岛素血症的影响。此外，还比较了 GIP 的作用与 GLP-1 的作用。用麻醉的雌性 NMRI 小鼠单独静脉内注射葡萄糖（1g/kg，n = 35）或葡萄糖与 GIP（50μg/kg，n = 12）。在接下来的 50 分钟内取样，并使用 C 肽和胰岛素浓度来重建 C 肽分泌率和胰岛素清除率。在先前的研究中，用 12 只小鼠给予 GLP-1（10μg/kg）；我们使用这些 GLP-1 结果来比较 GIP 与 GLP-1 的作用。C 肽分泌率在葡萄糖注射后 1 分钟达到峰值，两种肠促胰岛素激素明显增强了胰岛素释放过程的即时部分（GIP 的 1 分钟超基础分泌率为 20±2pmol/min，GLP-1 为 28±2pmol/min，而单独葡萄糖为 9±1pmol/min；P<0.001）。在给予增敏剂后 10 分钟内，C 肽分泌仍保持较高水平（P<0.0001），而从 20 分钟开始，3 种模式无法区分（P>0.2）。先前显示 GLP-1 可使胰岛素清除率缩短 46%，而 GIP 仅使胰岛素清除率缩短 21%（P=0.27），差异无统计学意义。因此，本研究表明，这两种肠促胰岛素激素通过优先作用于胰岛素分泌对葡萄糖刺激的即时反应，明显增强了小鼠的葡萄糖刺激胰岛素分泌。然而，GIP 的作用不如 GLP-1 有效。GIP 对胰岛素清除率的影响无明显降低。我们得出结论，GIP 在诱导小鼠葡萄糖刺激性高胰岛素血症方面的作用不如 GLP-1 强。
