McCullough A J, Miller L J, Service F J, Go V L
J Clin Endocrinol Metab. 1983 Feb;56(2):234-41. doi: 10.1210/jcem-56-2-234.
Gastric inhibitory polypeptide (GIP) is the leading candidate for gut hormonal augmentation of insulin release. The release of its subspecies (mol wt, 5000 and 7500) and the physiological action of total immunoreactive GIP (IR-GIP) were investigated during isotonic glucose infusions at 75, 225, and 465 mg/min in nine volunteers. Each dose was infused intraduodenally and iv in the same volunteer. Intestinal augmentation of insulin release occurred during the high dose intraduodenal glucose infusion (P less than 0.001) but not during the lower doses. An elevation of 17-20 mg/dl in plasma glucose was required before this insulinotropic effect occurred (P less than 0.001). At increments of plasma glucose above 17 mg/dl, the augmentation of gut-mediated insulin release was dependent on the degree of hyperglycemia (r = 0.81; P less than 0.01). At each dose of intraduodenally administered glucose, IR-GIP was elevated within 20-40 min (P less than 0.01), remaining at a steady level until the infusion was stopped. The release of IR-GIP was elevated within 20-40 min (P less than 0.01), remaining at a steady level until the infusion was stopped. The release of IR-GIP was proportional to the intestinal glucose load but was unchanged from the basal level during iv glucose studies. The attained IR-GIP levels remained constant in each study despite large variations over time in plasma glucose and insulin concentrations. During intestinal glucose infusion, 58.7 +/- 4.1% of IR-GIP was accounted for by the 5000 mol wt subspecies and 17.3 +/- 3.5% was accounted for by the 7500 mol wt subspecies, with the remaining immunoreactivity found in the void volume of a Sephadex G-50 column. Relative proportions remained constant throughout the 4-h study. Thus, during glucose stimulation, the total IR-GIP released 1) is proportional to the absorbable luminal stimulus, 2) is independent of ambient plasma insulin and glucose levels, 3) is composed predominantly of the 5000 mol wt form, and 4) requires an elevation in plasma glucose of 17-20 mg/dl before it augments insulin release, but then stimulates insulin release in a fashion linearly dependent upon the increment in plasma glucose.
胃抑制性多肽（GIP）是肠道激素增强胰岛素释放的主要候选物质。在9名志愿者以75、225和465毫克/分钟的速度进行等渗葡萄糖输注期间，研究了其亚种（分子量分别为5000和7500）的释放以及总免疫反应性GIP（IR - GIP）的生理作用。每种剂量均在同一名志愿者体内通过十二指肠内和静脉内输注。在高剂量十二指肠内葡萄糖输注期间出现了肠道对胰岛素释放的增强作用（P＜0.001），而低剂量时未出现。在这种促胰岛素作用发生之前，血浆葡萄糖需要升高17 - 20毫克/分升（P＜0.001）。当血浆葡萄糖升高超过17毫克/分升时，肠道介导的胰岛素释放增强取决于高血糖程度（r = 0.81；P＜0.01）。在每一次十二指肠内给予葡萄糖的剂量下，IR - GIP在20 - 40分钟内升高（P＜0.01），在输注停止前一直保持稳定水平。IR - GIP的释放在20 - 40分钟内升高（P＜0.01），在输注停止前一直保持稳定水平。IR - GIP的释放与肠道葡萄糖负荷成正比，但在静脉内葡萄糖研究期间与基础水平无变化。尽管血浆葡萄糖和胰岛素浓度随时间有很大变化，但在每项研究中达到的IR - GIP水平保持恒定。在肠道葡萄糖输注期间，58.7±4.1%的IR - GIP由分子量为5000的亚种构成，17.3±3.5%由分子量为7500的亚种构成，其余免疫反应性出现在葡聚糖G - 50柱的空体积中。在整个4小时的研究中相对比例保持恒定。因此，在葡萄糖刺激期间，释放的总IR - GIP：1）与可吸收的管腔刺激成正比；2）与周围血浆胰岛素和葡萄糖水平无关；3）主要由分子量为5000的形式构成；4）在增强胰岛素释放之前需要血浆葡萄糖升高17 - 20毫克/分升，但随后以与血浆葡萄糖升高呈线性相关的方式刺激胰岛素释放。
