Role of Fat Hydrolysis in Regulating Glucagon-Like Peptide-1 Secretion

被引:109
作者
Beglinger, Svetlana [3 ]
Drewe, Juergen [2 ,3 ]
Schirra, Joerg [4 ]
Goeke, Burkhard [4 ]
D'Amato, Massimo [5 ,6 ]
Beglinger, Christoph [1 ,2 ,3 ]
机构
[1] Univ Basel, Univ Hosp, Div Gastroenterol, Dept Gastroenterol, CH-4031 Basel, Switzerland
[2] Univ Basel, Univ Hosp, Clin Res Ctr, CH-4031 Basel, Switzerland
[3] Univ Basel, Univ Hosp, Dept Res, CH-4031 Basel, Switzerland
[4] Univ Basel, Univ Hosp, Clin Res Unit, CH-4031 Basel, Switzerland
[5] Univ Munich, Dept Internal Med 2, D-80539 Munich, Germany
[6] Rotta Pharma Spa, I-20052 Monza, Italy
基金
瑞士国家科学基金会;
关键词
ANTROPYLORODUODENAL MOTILITY; HEALTHY-MEN; FOOD-INTAKE; CHOLECYSTOKININ RELEASE; DUODENAL GLUCOSE; HORMONE-RELEASE; VAGAL AFFERENTS; ENERGY-INTAKE; CHAIN-LENGTH; HUMANS;
D O I
10.1210/jc.2009-1062
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Glucagon-like peptide-1 (GLP-1) is produced by specialized cells in the gut and secreted in response to carbohydrates and lipids. The mechanisms regulating fat-stimulated GLP-1 release have, however, not been clarified in detail. Aim: We aimed to investigate the effect of intraduodenal (ID) fat hydrolysis on GLP-1 release and test whether the signal is mediated through cholecystokinin (CCK)-1 receptors. Design and Setting: Thirty-four healthy, male ambulatory volunteers were studied in three consecutive, randomized, double blind, crossover studies. Intervention: There were three interventions: 1) 12 subjects received an ID fat infusion with or without orlistat, an irreversible inhibitor of gastrointestinal lipases, in comparison with vehicle; 2) 12 subjects received ID sodium oleate (C18:1), ID sodium caprylate (C8:0), or ID vehicle; and 3) 10 subjects received ID sodium oleate with and without the CCK-1 receptor antagonist dexloxiglumide or ID vehicle plus iv saline (placebo). The effect of these treatments on GLP-1 concentrations and CCK release was quantified. Results: The following results were reached: 1) ID fat induced significant increase in GLP-1 concentrations ( P < 0.004), and inhibition of fat hydrolysis by orlistat abolished this effect; 2) sodium oleate significantly stimulated GLP-1 release (P < 0.008), whereas sodium caprylate was ineffective compared with controls; and 3) dexloxiglumide administration abolished the effect of sodium oleate on GLP-1. ID fat or sodium oleate significantly stimulated plasma CCK (P < 0.006 and P < 0.004) compared with saline, whereas sodium caprylate did not. Conclusion: Generation of long-chain fatty acids through hydrolysis of fat is a critical step for fat-induced stimulation of GLP-1 in humans; the signal is mediated via CCK release and CCK-1 receptors. (J Clin Endocrinol Metab 95: 879-886, 2010)
引用
收藏
页码:879 / 886
页数:8
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