Regulation of Islet Hormone Release and Gastric Emptying by Endogenous Glucagon-Like Peptide 1 after Glucose Ingestion
Regulation of Islet Hormone Release and Gastric Emptying by Endogenous Glucagon-Like Peptide 1 after Glucose Ingestion
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DOI：
10.1210/jc.2008-0605
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发表时间：
2008-12-01
影响因子：
5.8
通讯作者：
D'Alessio, David A.
中科院分区：
文献类型：
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作者：
Salehi, Marzieh;Vahl, Torsten P.;D'Alessio, David A.
背景：外源性给予胰升糖素样肽(GLP)-1可通过刺激胰岛素分泌、抑制胰高血糖素分泌和延迟胃排空来改善糖耐量。目前尚不清楚这些影响中的哪一种参与了内源性GLP-1控制血糖的作用。为了确定内源性GLP-1对胰岛细胞功能和胃排空功能的影响，我们在摄入葡萄糖之前和期间分别用exendin-[9-39]和不用exendin-[9-39](Ex-9)阻断GLP-1受体阻断血糖。方法：10名健康受试者参加了两个实验，一个为对照组，一个为750 pm/kg。Min Ex-9.受试者摄入75g含D-木糖和(13)C-葡萄糖的口服葡萄糖溶液，同时他们的血糖水平保持在约8.9 mmoL/L。结果：两项研究中仅高血糖时的血浆胰岛素水平相似(对照组，282.5+/-42vs.Ex-9,263.8+/-59pmoL/L)，但在摄入葡萄糖后，Ex-9降低了约30%(对照组，1154+/-203vs.Ex-9,835+/-120pmol/L；P<；0.05)。阻断内源性GLP-1的作用导致餐后胰高血糖素浓度增加约80%。血中D-木糖的摄入不受Ex-9的影响，提示餐后GLP-1的分泌对口服葡萄糖的胃排空影响很小。结论：GLP-1在健康人中是一种处于适度生理血糖水平的胰岛素。GLP-1调节糖耐量的主要作用是通过影响胰岛激素而不是胃排空来实现的。(J Clin Endocrinol Metab 93：4909-4916,2008)
Background: Exogenous administration of glucagon-like peptide (GLP)-1 improves glucose tolerance by stimulation of insulin secretion, inhibition of glucagon secretion, and delay of gastric emptying. It is not known which of these effects is involved in the action of endogenous GLP-1 to control blood glucose. To determine the role of endogenous GLP-1 on islet cell function and gastric emptying independent of variable glycemia, we clamped blood glucose before and during glucose ingestion with and without GLP-1 receptor blockade with exendin-[9-39] (Ex-9).Methods: There were 10 healthy subjects that participated in two experiments each, one a control and one with infusion of 750 pm/kg . min Ex-9. Subjects consumed 75 g oral glucose solution mixed with D-xylose and (13)C-glucose while their blood glucose levels were held fixed at approximately 8.9 mmol/liter.Results: Plasma insulin levels during hyperglycemia alone were similar in the two studies (control, 282.5 +/- 42 vs. Ex-9, 263.8 +/- 59 pmol/liter) but were reduced by approximately 30% by Ex-9 after glucose ingestion (control, 1154 +/- 203 vs. Ex-9, 835 +/- 120 pmol/liter; P < 0.05). Blocking the action of endogenous GLP-1 caused an approximate 80% increase in postprandial glucagon concentrations. The appearance of ingested D-xylose in the blood was not affected by Ex-9, suggesting that postprandial secretion of GLP-1 has only minimal effects on gastric emptying of oral glucose.Conclusions: These findings indicate that GLP-1 is an incretin in healthy humans at modestly supraphysiological blood glucose levels. The primary effect of GLP-1 to regulate oral glucose tolerance is mediated by effects on islet hormones and not on gastric emptying. (J Clin Endocrinol Metab 93: 4909-4916, 2008)