Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects
Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects
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DOI：
10.1016/s0167-0115(03)00111-3
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发表时间：
2003-07-15
影响因子：
--
通讯作者：
Holst, JJ
中科院分区：
文献类型：
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作者：
Vilsboll, T;Krarup, T;Holst, JJ
胰升糖素样肽-1(GLP-1)和葡萄糖依赖的促胰岛素多肽(GIP)都是调节餐后胰岛素分泌的胰岛素激素。然而，在正常生理条件下，它们在这方面的相对重要性尚不清楚，本研究的目的是评估这一点。8名健康男性志愿者(平均年龄：23(20-25)岁；平均体重指数：22.2(19.3-25.4)kg/m(2))参与了在空腹血糖水平、6和7 mmol/L水平下逐步阻断葡萄糖的研究。生理剂量的GIP(1.5pmoL/kg/min)、GLP-1(7-36)酰胺(0.33pmoL/kg/min)或生理盐水在每个血糖水平下输注三次30min，每次输注间隔1h。在另一天，进行了标准膳食测试(566千卡)。餐后30min，胰岛素浓度达到峰值，达223+/-27pmol/L。葡萄糖+生理盐水仅引起胰岛素浓度轻微升高。GLP-1和GIP在空腹血糖水平和6 mmoL/L时均引起显著升高，在7 mmoL/L时进一步升高，且GLP-1的作用超过GIP。在GIP钳夹期间的3个输注期(60、150和240min)结束时，胰岛素浓度分别为535、798和113+/-15pmol/L。相应的结果分别为47+/-7、95+/-10和171+/-21pmol/L。C-肽反应相似。钳夹试验期间，总的和完整的胰升糖素激素浓度高于膳食试验，但在生理范围内。单纯葡萄糖输注显著抑制胰高血糖素的分泌，GLP-1可进一步抑制GLP-1的分泌，但GIP对此无明显影响。我们的结论是，在正常的生理血糖水平下，胰升糖素样肽-1和依赖于葡萄糖-9的胰岛素样多肽对人类的胰岛素效应的贡献几乎相同，因为它们在浓度和效力上的差异超过了彼此。(C)2003 Elsevier Science B.V.保留所有权利。
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are both incretin hormones regulating postprandial insulin secretion. Their relative importance in this respect under normal physiological conditions is unclear, however, and the aim of the present investigation was to evaluate this. Eight healthy male volunteers (mean age: 23 (range 20-25) years; mean body mass index: 22.2 (range 19.3-25.4) kg/m(2)) participated in studies involving stepwise glucose clamping at fasting plasma glucose levels and at 6 and 7 mmol/l. Physiological amounts of either GIP (1.5 pmol/kg/min), GLP-1(7-36)amide (0.33 pmol/kg/min) or saline were infused for three periods of 30 min at each glucose level, with 1 h "washout" between the infusions. On a separate day, a standard meal test (566 kcal) was performed. During the meal test, peak insulin concentrations were observed after 30 min and amounted to 223 +/- 27 pmol/l. Glucose+ saline infusions induced only minor increases in insulin concentrations. GLP-1 and GIP infusions induced significant and similar increases at fasting glucose levels and at 6 mmol/l. At 7 mmol/l, further increases were seen, with GLP-1 effects exceeding those of GIP. Insulin concentrations at the end of the three infusion periods (60, 150 and 240 min) during the GIP clamp amounted to 53 5, 79 8 and 113 +/- 15 pmol/l, respectively. Corresponding results were 47 +/- 7, 95 +/- 10 and 171 +/- 21 pmol/l, respectively, during the GLP-1 clamp. C-peptide responses were similar. Total and intact incretin hormone concentrations during the clamp studies were higher compared to the meal test, but within physiological limits. Glucose infusion alone significantly inhibited glucagon secretion, which was further inhibited by GLP-1 but not by GIP infusion. We conclude that during normal physiological plasma glucose levels, glucagon-like peptide-1 and glucose-9 dependent insulinotropic polypeptide contribute nearly equally to the incretin effect in humans, because their differences in concentration and potency outweigh each other. (C) 2003 Elsevier Science B.V. All rights reserved.