| Title | Role of Fat Hydrolysis in Regulating Glucagon-Like Peptide-1 Secretion. | | Author(s) | Beglinger S, Drewe J, Schirra J, Göke B, D'Amato M, Beglinger C | | Institution | Department of Gastroenterology and Clinical Research Centre (J.D., C.B.), Department of Research (S.B., J.D., C.B.), Clinical Research Unit (J.S., B.G.), University Hospital, CH-4031 Basel, Switzerland; Department of Internal Medicine II, Ludwig-Maximilians University, 80539 Munich, Germany; and Rotta Pharma Spa (M.D.), 20052 Monza, Italy. | | Source | J Clin Endocrinol Metab 2009 Oct 16. | | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19837920 |
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