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首页> 外文期刊>American Journal of Physiology >Reduction of hepatic insulin clearance after oral glucose ingestion is not mediated by glucagon-like peptide 1 or gastric inhibitory polypeptide in humans.
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Reduction of hepatic insulin clearance after oral glucose ingestion is not mediated by glucagon-like peptide 1 or gastric inhibitory polypeptide in humans.

机译：口服葡萄糖摄入后，肝脏中胰岛素清除率的降低不是由人体内胰高血糖素样肽1或胃抑制性多肽介导的。

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摘要

Changes in hepatic insulin clearance can occur after oral glucose or meal ingestion. This has been attributed to the secretion and action of gastric inhibitory polypeptide (GIP) and glucagon-like peptide (GLP)-1. Given the recent availability of drugs based on incretin hormones, such clearance effects may be important for the future treatment of type 2 diabetes. Therefore, we determined insulin clearance in response to endogenously secreted and exogenously administered GIP and GLP-1. Insulin clearance was estimated from the molar C-peptide-to-insulin ratio calculated at basal conditions and from the respective areas under the curve after glucose, GIP, or GLP-1 administration. Oral glucose administration led to an approximately 60% reduction in the C-peptide-to-insulin ratio (P < 0.0001), whereas intravenous glucose administration had no effect (P = 0.09). The endogenous secretion of GIP or GLP-1 was unrelated to the changes in insulin clearance. The C-peptide-to-insulin ratio was unchanged after the intravenous administration of GIP or GLP-1 in the fasting state (P = 0.27 and P = 0.35, respectively). Likewise, infusing GLP-1 during a meal course did not alter insulin clearance (P = 0.87). An inverse nonlinear relationship was found between the C-peptide-to-insulin ratio and the integrated insulin levels after oral and during intravenous glucose administration. Insulin clearance is reduced by oral but not by intravenous glucose administration. Neither GIP nor GLP-1 has significant effects on insulin extraction. An inverse relationship between insulin concentrations and insulin clearance suggests that the secretion of insulin itself determines the rate of hepatic insulin clearance.
机译：口服葡萄糖或进餐后，肝脏胰岛素清除率可能发生变化。这归因于胃抑制性多肽（GIP）和胰高血糖素样肽（GLP）-1的分泌和作用。考虑到最近基于肠降血糖素激素的药物的可获得性，这种清除作用对于将来治疗2型糖尿病可能很重要。因此，我们确定响应于内源性分泌和外源性给予的GIP和GLP-1的胰岛素清除率。胰岛素清除率是根据基础条件下计算出的C肽与胰岛素的摩尔比以及施用葡萄糖，GIP或GLP-1后曲线下的各个区域估算的。口服葡萄糖导致C肽与胰岛素之比降低约60％（P <0.0001），而静脉葡萄糖给药则无影响（P = 0.09）。 GIP或GLP-1的内源性分泌与胰岛素清除率的变化无关。在空腹状态下静脉内施用GIP或GLP-1后，C肽与胰岛素的比例没有变化（分别为P = 0.27和P = 0.35）。同样，在进餐过程中注入GLP-1不会改变胰岛素清除率（P = 0.87）。在口服和静脉内葡萄糖给药后，C肽与胰岛素的比例与胰岛素的积分水平之间存在反比的非线性关系。口服可降低胰岛素清除率，但静脉内施用葡萄糖则不会降低。 GIP和GLP-1都不会对胰岛素提取产生明显影响。胰岛素浓度与胰岛素清除率之间存在反比关系，表明胰岛素本身的分泌决定了肝脏胰岛素清除率。

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