Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
J Clin Endocrinol Metab. 2020 Mar 1;105(3). doi: 10.1210/clinem/dgz175.
The actions of both endogenous incretin hormones during a meal have not previously been characterized.
Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility.
Randomized, double-blinded, placebo-controlled, crossover design.
On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min).
Twelve healthy male volunteers.
Infusions of the GIP receptor antagonist GIP(3-30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9-39)NH2 (0-20 min: 1000 pmol/kg/min; 20-270 min: 450 pmol/kg/min), GIP(3-30)NH2+exendin(9-39)NH2, or placebo/saline.
Baseline-subtracted area under the curve (bsAUC) of C-peptide.
Infusion of GIP(3-30)NH2+exendin(9-39)NH2 significantly increased plasma glucose excursions (bsAUC: 261 ± 142 mmol/L × min) during the liquid mixed meals compared with GIP(3-30)NH2 (180 ± 141 mmol/L × min; P = 0.048), exendin(9-39)NH2 (171 ± 114 mmol/L × min; P = 0.046), and placebo (116 ± 154 mmol/L × min; P = 0.015). Correspondingly, C-peptide:glucose ratios during GIP(3-30)NH2+exendin(9-39)NH2 infusion were significantly lower than during GIP(3-30)NH2 (P = 0.0057), exendin(9-39)NH2 (P = 0.0038), and placebo infusion (P = 0.014). GIP(3-30)NH2 resulted in significantly lower AUCs for glucagon than exendin(9-39)NH2 (P = 0.0417). Gallbladder ejection fraction was higher during GIP(3-30)NH2 compared with placebo (P = 0.004). For all interventions, energy expenditure and respiratory quotient were similar.
Endogenous GIP and GLP-1 lower postprandial plasma glucose excursions and stimulate insulin secretion but only endogenous GIP affects gallbladder motility. The two incretin hormones potentiate each other's effects in the control of postprandial glycemia in healthy men.
此前尚未描述过内源性肠降血糖素激素在进餐期间的作用。
使用特定的受体拮抗剂，我们研究了内源性葡萄糖依赖性胰岛素促分泌多肽（GIP）和胰高血糖素样肽 1（GLP-1）对餐后葡萄糖代谢、能量消耗和胆囊运动的单独和联合作用。
随机、双盲、安慰剂对照、交叉设计。
在四个不同的日子里，进行四个液体混合餐测试（1894 kJ），持续 270 分钟（min）。
12 名健康男性志愿者。
给予 GIP 受体拮抗剂 GIP(3-30)NH2（800 pmol/kg/min）、GLP-1 受体拮抗剂 exendin(9-39)NH2（0-20 min：1000 pmol/kg/min；20-270 min：450 pmol/kg/min）、GIP(3-30)NH2+exendin(9-39)NH2 或安慰剂/生理盐水输注。
C 肽的基础值校正后曲线下面积（bsAUC）。
与 GIP(3-30)NH2（180±141mmol/L×min；P=0.048）、exendin(9-39)NH2（171±114mmol/L×min；P=0.046）和安慰剂（116±154mmol/L×min；P=0.015）相比，GIP(3-30)NH2+exendin(9-39)NH2 输注显著增加了液体混合餐期间的血浆葡萄糖波动（bsAUC：261±142mmol/L×min）。相应地，GIP(3-30)NH2+exendin(9-39)NH2 输注时的 C 肽/血糖比值明显低于 GIP(3-30)NH2（P=0.0057）、exendin(9-39)NH2（P=0.0038）和安慰剂输注（P=0.014）。GIP(3-30)NH2 导致的胰高血糖素 AUC 明显低于 exendin(9-39)NH2（P=0.0417）。与安慰剂相比，GIP(3-30)NH2 使胆囊排空分数更高（P=0.004）。对于所有干预措施，能量消耗和呼吸商相似。
内源性 GIP 和 GLP-1 降低餐后血浆葡萄糖波动并刺激胰岛素分泌，但只有内源性 GIP 影响胆囊运动。两种肠降血糖素激素在健康男性的餐后血糖控制中具有协同作用。
