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Role of fat hydrolysis in regulating glucagon-like Peptide-1 secretion

Beglinger, Svetlana and Drewe, Juergen and Schirra, Joerg and Göke, Burkhard and D'Amato, Massimo and Beglinger, Christoph. (2010) Role of fat hydrolysis in regulating glucagon-like Peptide-1 secretion. Journal of clinical endocrinology and metabolism, Vol. 95, H. 2. pp. 879-886.

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Official URL: http://edoc.unibas.ch/dok/A5840272

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Clinical Pharmacology (Drewe)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Gastroenterology (Beglinger)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
UniBasel Contributors:Beglinger, Christoph and Drewe, Jürgen
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Thomas
ISSN:0021-972X
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:31 Dec 2015 10:51
Deposited On:07 Dec 2012 13:02

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