Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study

被引:109
作者
Bergmann, Natasha C. [1 ,2 ,3 ]
Lund, Asger [1 ,4 ]
Gasbjerg, Lwrke S. [1 ,3 ,5 ]
Meessen, Emma C. E. [6 ]
Andersen, Maria M. [1 ]
Bergmann, Sigrid [1 ]
Hartmann, Bolette [3 ,5 ]
Holst, Jens J. [3 ,5 ]
Jessen, Lene [2 ]
Christensen, Mikkel B. [1 ,7 ,8 ]
Vilsboll, Tina [1 ,8 ]
Knop, Filip K. [1 ,5 ,8 ]
机构
[1] Gentofte Univ Hosp, Steno Diabet Ctr Copenhagen, Clin Metab Physiol, Kildegardsvej 28, DK-2900 Hellerup, Denmark
[2] Zealand Pharma AS, Dept Vivo Pharmacol, Glostrup, Denmark
[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Biomed Sci, Copenhagen, Denmark
[4] Univ Copenhagen, Gentofte Hosp, Dept Med, Hellerup, Denmark
[5] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Fac Hlth & Med Sci, Copenhagen, Denmark
[6] Univ Amsterdam, Acad Med Ctr, Dept Endocrinol & Metab, Amsterdam UMC, Amsterdam, Netherlands
[7] Univ Copenhagen, Bispebjerg Hosp, Dept Clin Phaimacol, Copenhagen, Denmark
[8] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark
关键词
Appetite; Dual receptor agonism; Energy expenditure; Energy intake; Glucagon-like peptide 1; Glucose-dependent insulinotropic polypeptide; Obesity; Overweight; GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; GASTRIC-INHIBITORY POLYPEPTIDE; TYPE-2; DIABETIC-PATIENTS; ELIMINATION RATES; INCRETIN HORMONE; 7-36; AMIDE; GLUCOSE; HEALTHY; METABOLISM;
D O I
10.1007/s00125-018-4810-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis Glucagon-like peptide 1 (GLP-1) reduces appetite and energy intake in humans, whereas the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), seems to have no effect on eating behaviour. Interestingly, studies in rodents have shown that concomitant activation of GIP and GLP-1 receptors may potentiate the satiety-promoting effect of GLP-1, and a novel dual GLP-1/GIP receptor agonist was recently shown to trigger greater weight losses compared with a GLP-1 receptor agonist in individuals with type 2 diabetes. The aim of this study was to delineate the effects of combined GIP and GLP1 receptor activation on energy intake, appetite and resting energy expenditure in humans. Methods We examined 17 overweight/obese men in a crossover design with 5 study days. On day 1, a 50 g OGTT was performed; on the following 4 study days, the men received an isoglycaemic i. v. glucose infusion (IIGI) plus saline (154 mmol/l NaCl; placebo), GIP (4 pmol kg-1 min-1), GLP-1 (1 pmol kg-1 min-1) or GIP+ GLP-1 (4 and 1 pmol kg-1 min-1, respectively). All IIGIs were performed in a randomised order blinded for the participant and the investigators. The primary endpoint was energy intake as measured by an ad libitum meal after 240 min. Secondary endpoints included appetite ratings and resting energy expenditure, as well as insulin, C-peptide and glucagon responses. Results Energy intake was significantly reduced during IIGI+ GLP-1 compared with IIGI+ saline infusion (2715 +/- 409 vs 4483 +/- 568 kJ [ mean +/- SEM, n = 17], p = 0.014), whereas there were no significant differences in energy intake during IIGI+ GIP (4062 +/- 520 kJ) or IIGI+ GIP+ GLP-1 (3875 +/- 451 kJ) infusion compared with IIGI+ saline (p = 0.590 and p = 0.364, respectively). Energy intake was higher during IIGI+ GIP+ GLP-1 compared with IIGI+ GLP-1 infusion (p = 0.039). Conclusions/interpretation While GLP-1 infusion lowered energy intake in overweight/obese men, simultaneous GIP infusion did not potentiate this GLP-1-mediated effect.
引用
收藏
页码:665 / 675
页数:11
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