Effect of Oxyntomodulin, Glucagon, GLP-1, and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite, and Resting Energy Expenditure
Effect of Oxyntomodulin, Glucagon, GLP-1, and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite, and Resting Energy Expenditure
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DOI：
10.1210/jc.2015-2335
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发表时间：
2015-12-01
影响因子：
5.8
通讯作者：
Vilsboll, Tina
中科院分区：
文献类型：
--
作者：
Bagger, Jonatan Ising;Holst, Jens Juul;Vilsboll, Tina
背景：胃泌酸调节素是一种具有降低体重潜力的胰高血糖素原。它与胰高血糖素样肽-1（GLP-1）受体和胰高血糖素受体结合;然而，降低体重效果背后的机制仍然难以捉摸。目的：我们想描述单独和联合GLP-1受体和胰高血糖素受体激活对胃泌酸调节素降低体重机制的贡献。设计：这是一项双盲、随机、交叉研究。设置：本研究在一个专门的研究单位进行。参与者：15名年轻健康男性志愿者（年龄22 [范围18-32] y;体重指数23 [21-26] kg/m2;空腹血糖5.1 [4.4-5.4] mmol/L;糖化血红蛋白A1 c 40（37-42）mmol/mol）。输注生理盐水期间的5次4小时流质饮食试验，GLP-1（1 pmol x kg（-1）x min（-1）），胰高血糖素（0.86 pmol x kg（-1）x min（-1）），胃泌酸调节素（3 pmol x kg（-1）x min（-1））或胰高血糖素+ GLP-1主要结果测量：我们评估了静息能量消耗，（测量为摄氧量、胃排空（GE）、复合食欲评分（CAS）和食物摄入。胃泌酸调节素、GLP-1和GLP-1-胰高血糖素减慢GE并降低CAS，而胰高血糖素不影响GE和CAS。与生理盐水相比，所有输注均引起相似的摄食量减少（总摄入量（g [95%置信区间]）、生理盐水811 [729，892]、GLP-1 669 [586，750]、胰高血糖素686 [604，768]、胃泌酸调节素689 [608，771]和胰高血糖素-GLP-1 688 [606，769]）。氧摄取量没有改变显着从基线在任何肽输液相比salines.Conclusions：胃泌酸调节素，GLP-1，胰高血糖素减少食物摄入量，但没有额外的影响相结合的GLP-1和胰高血糖素。
Context: The gut hormone, oxyntomodulin, is a proglucagon product with body weight-lowering potential. It binds to both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor; however, the mechanism behind the body weight-lowering effect remains elusive.Objective: We wanted to delineate the contributions of separate and combined GLP-1 receptor and glucagon receptor activation to the body weight-reducing mechanisms of oxyntomodulin.Design: This was a double-blinded, randomized, crossover study.Setting: The study was conducted at a specialized research unit.Participants: Fifteen young healthy male volunteers (aged 22 [range 18-32] y; body mass index 23 [21-26] kg/m(2); fasting plasma glucose 5.1 [4.4-5.4] mmol/L; and glycated hemoglobin A1c 40 (37-42) mmol/mol).Interventions: Five 4-hour liquid meal tests during the infusion of saline, GLP-1 (1 pmol x kg(-1) x min(-1)), glucagon (0.86 pmol x kg(-1) x min(-1)), oxyntomodulin (3 pmol x kg(-1) x min(-1)), or glucagon + GLP-1 (same doses).Main Outcome Measures: We evaluated resting energy expenditure (measured as oxygen uptake, gastric emptying (GE), composite appetite scores (CAS), and food intake.Results: Oxyntomodulin, GLP-1, and GLP-1-glucagon slowed GE and reduced CAS, whereas glucagon did not affect GE and CAS. All infusions caused a similar decrease in food intake compared with saline (total intake (g [95% confidence interval]), saline 811 [729, 892], GLP-1 669 [586, 750], glucagon 686 [604, 768], oxyntomodulin 689 [608, 771], and glucagon-GLP-1 688 [606, 769]). Oxygen uptake did not change significantly from baseline in response to any peptide infusion compared with saline.Conclusions: Oxyntomodulin, GLP-1, and glucagon decreased food intake but with no additional effect of combining GLP-1 and glucagon.