Discipline of Acute Care Medicine, University of Adelaide, Adelaide, AustraliaDepartment of Critical Care Services, Royal Adelaide Hospital, Adelaide, AustraliaCentre for Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, Adelaide, Australia
Centre for Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, Adelaide, AustraliaDiscipline of Medicine, University of Adelaide, Adelaide, Australia.
Diabetes Care. 2014 Jun;37(6):1509-15. doi: 10.2337/dc13-1813. Epub 2014 Mar 5.
Exogenous GLP-1 slows gastric emptying in health and diabetes leading to diminished glycemic excursions. Gastric emptying is markedly accelerated by hypoglycemia. The primary objective was to determine whether GLP-1 attenuates the acceleration of gastric emptying induced by hypoglycemia.
Ten healthy volunteers were studied on four separate days in a randomized double-blind fashion. Blood glucose was stabilized using a glucose/insulin clamp at hypoglycemia (2.6 mmol/L on two occasions [hypo]) or euglycemia (6.0 mmol/L on two occasions [eu]) between T = -15 and 45 min before clamping at 6.0 mmol/L until 180 min. During hypoglycemia and euglycemia, subjects received intravenous GLP-1 (1.2 pmol/kg/min) or placebo. At T = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq (99m)Tc-sulfur-colloid and 3 g of 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from T = 0 to 180 min and serum 3-OMG taken at 15-min intervals. The areas under the curve for gastric emptying and 3-OMG concentration were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests.
Gastric emptying was accelerated during hypoglycemia (hypo/placebo vs. eu/placebo; P < 0.001), as was glucose absorption (P < 0.03). GLP-1 slowed emptying during euglycemia (eu/placebo vs. eu/GLP-1; P < 0.001). However, hypoglycemia-induced acceleration of gastric emptying on placebo was markedly diminished by GLP-1 (hypo/placebo vs. hypo/GLP-1; P < 0.008), as was glucose absorption (P < 0.01).
Acute administration of exogenous GLP-1 attenuates, but does not abolish, the acceleration of gastric emptying by insulin-induced hypoglycemia in healthy subjects.
外源性 GLP-1 可减缓健康人和糖尿病患者的胃排空速度，从而减少血糖波动。低血糖会显著加速胃排空。主要目的是确定 GLP-1 是否能减弱低血糖引起的胃排空加速。
10 名健康志愿者在 4 天内以随机、双盲的方式进行研究。通过血糖/胰岛素钳夹将血糖稳定在低血糖（2.6mmol/L，2 次[hypo]）或正常血糖（6.0mmol/L，2 次[eu]），在 6.0mmol/L 钳夹前 15 分钟至 45 分钟，直至 180 分钟。在低血糖和正常血糖期间，受试者接受静脉注射 GLP-1（1.2pmol/kg/min）或安慰剂。在 T=0 分钟时，受试者摄入 100g 牛肉肉末，标记有 20MBq（99m）Tc-硫胶体和 3g 3-O-甲基葡萄糖（3-OMG），这是葡萄糖吸收的标志物。从 T=0 分钟到 180 分钟进行胃排空闪烁扫描，并在 15 分钟间隔采集血清 3-OMG。使用单向重复测量方差分析和 Bonferroni-Holm 调整后的事后检验分析胃排空和 3-OMG 浓度的曲线下面积。
低血糖期间胃排空加速（hypo/placebo vs. eu/placebo；P<0.001），葡萄糖吸收也加速（P<0.03）。GLP-1 在正常血糖期间减缓排空（eu/placebo vs. eu/GLP-1；P<0.001）。然而，在 GLP-1 存在下，低血糖引起的胃排空加速显著减弱（hypo/placebo vs. hypo/GLP-1；P<0.008），葡萄糖吸收也减弱（P<0.01）。
在健康受试者中，急性给予外源性 GLP-1 可减弱胰岛素诱导的低血糖引起的胃排空加速，但不能完全消除。
