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Title: Secretion of cholecystokinin and its physiological role in the control of satiety in humans
Author: Ballinger, Anne
ISNI:       0000 0001 3441 8083
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1995
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A sensitive and specific radioimmunoassay (RIA) has been developed for measurement of plasma concentrations of cholecystokinin (CCK). A previously described CCK bioassay has been established and a direct comparison made of plasma CCK concentrations measured with the bioassay and RIA. These assays have been used to investigate secretion of CCK and its role in the control of satiety in healthy human volunteers. Release of CCK was examined in response to an isocaloric load of fat or glucose administered orally. Fat, but not glucose, produced a significant increase in plasma concentrations of CCK compared to fasting values. Similar experiments were performed with L- and D-phenylalanine and it was shown that only L-phenylalanine (L-Phe) released CCK and produced peak plasma CCK concentrations similar to those seen after ingestion of a meal of mixed nutrients. A rapid intravenous infusion of a mixture of L-amino acids increased plasma concentrations of CCK and in addition, promoted gallbladder contraction. The rate of amino acid infusion as well as the amount given determined the extent of gallbladder contraction and release of CCK. Two approaches have been used to investigate the physiological role of CCK in control of food intake in humans. As shown in earlier experiments L-Phe, but not D-Phe, increases endogenous secretion of CCK from duodenal endocrine cells. An oral load of L-Phe administered 20 minutes before a test meal significantly increased plasma CCK concentrations and reduced energy intake during the meal compared to energy intake after placebo. D-Phe did not release CCK or reduce energy intake compared to placebo. These results showed that release of endogenous CCK by L-Phe was associated with a reduction in food intake and provided indirect evidence that CCK is an important satiety peptide in humans. In a subsequent study subjects received an intravenous infusion of saline or synthetic CCK-8 to reproduce physiological postprandial plasma concentrations. Twenty five minutes after the start of the infusion subjects were presented with a test meal. Energy intake was significantly less during CCK infusion than during saline infusion. Thus these two series of experiments provide support that CCK is a physiological satiety hormone in humans. Finally the effect of activation of serotonergic (5-hydroxytryptamine, 5-HT) nerves on CCK release was investigated. Oral administration of dexfenfluramine, which enhances 5-HT release from nerve terminals, did not increase plasma concentrations of CCK. It seems unlikely therefore that release of peripheral CCK mediates the reduction in food intake which is induced by dexfenfluramine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine