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Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man. Feedback control of cholecystokinin and gastrin secretion.
Eur J Clin Invest. 1991 Oct; 21(5):501-11.EJ

Abstract

The effect of the potent specific cholecystokinin (CCK) receptor antagonist loxiglumide on meal-stimulated plasma concentrations of CCK, gastrin, pancreatic polypeptide (PP), neurotensin, glucose-dependent insulinotropic polypeptide (GIP), insulin and C peptide was investigated in a placebo-controlled study in 10 healthy male volunteers. Intravenous infusion of loxiglumide (10 mg kg-1 h-1) significantly augmented integrated incremental IR-CCK levels 7.3-fold after stimulation by a standard breakfast (504 +/- 54 vs 3.665 +/- 365 pmol-1 135 min-1, P less than 0.001), as measured by a specific CCK radioimmunoassay. Basal IR-CCK concentrations were not affected by administration of loxiglumide. Oral treatment with bile acids (2 g ursodeoxycholic acid plus 2 g chenodeoxycholic acid) together with the meal abolished this augmentation, whereas high-dose substitution with pancreatic enzymes (4.2 g pancreatin) reduced elevated IR-CCK levels by only 38%. CCK-like bioactivity, determined by a bioassay using rat pancreatic acini, was not detectable in all samples that contained loxiglumide at plasma concentrations of 100-250 micrograms ml-1. Plasma gastrin concentrations in response to the breakfast were elevated 3.2-fold during loxiglumide infusion and not influenced by substitution with bile acids or pancreatic enzymes. Meal-stimulated integrated incremental plasma PP concentrations were significantly suppressed (55-65% inhibition, P less than 0.01) by loxiglumide. Infusion of the CCK receptor antagonist only slightly increased postprandial peak plasma glucose, insulin and C-peptide levels, whereas GIP and neurotensin levels were not significantly influenced. These findings suggest: (i) CCK secretion is under feedback control by intraduodenal bile acids and to a lesser extent by pancreatic enzymes; (ii) simultaneous extraction of CCK and loxiglumide results in circulating plasma CCK-like bioactivity of zero; (iii) gastrin secretion is feedback controlled via an indirect mechanism probably involving CCK-induced somatostatin secretion; (iv) release of PP is under inhibitory control of CCK; (v) CCK does not play a major role as insulinotropic hormone in the entero-insular axis in humans.

Authors+Show Affiliations

Department of Medicine, University Hospital, Georg August University, Göttingen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1752290

Citation

Schmidt, W E., et al. "Cholecystokinin Receptor Antagonist Loxiglumide Modulates Plasma Levels of Gastro-entero-pancreatic Hormones in Man. Feedback Control of Cholecystokinin and Gastrin Secretion." European Journal of Clinical Investigation, vol. 21, no. 5, 1991, pp. 501-11.
Schmidt WE, Creutzfeldt W, Höcker M, et al. Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man. Feedback control of cholecystokinin and gastrin secretion. Eur J Clin Invest. 1991;21(5):501-11.
Schmidt, W. E., Creutzfeldt, W., Höcker, M., Nustede, R., Choudhury, A. R., Schleser, A., Rovati, L. C., & Fölsch, U. R. (1991). Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man. Feedback control of cholecystokinin and gastrin secretion. European Journal of Clinical Investigation, 21(5), 501-11.
Schmidt WE, et al. Cholecystokinin Receptor Antagonist Loxiglumide Modulates Plasma Levels of Gastro-entero-pancreatic Hormones in Man. Feedback Control of Cholecystokinin and Gastrin Secretion. Eur J Clin Invest. 1991;21(5):501-11. PubMed PMID: 1752290.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man. Feedback control of cholecystokinin and gastrin secretion. AU - Schmidt,W E, AU - Creutzfeldt,W, AU - Höcker,M, AU - Nustede,R, AU - Choudhury,A R, AU - Schleser,A, AU - Rovati,L C, AU - Fölsch,U R, PY - 1991/10/1/pubmed PY - 1991/10/1/medline PY - 1991/10/1/entrez SP - 501 EP - 11 JF - European journal of clinical investigation JO - Eur J Clin Invest VL - 21 IS - 5 N2 - The effect of the potent specific cholecystokinin (CCK) receptor antagonist loxiglumide on meal-stimulated plasma concentrations of CCK, gastrin, pancreatic polypeptide (PP), neurotensin, glucose-dependent insulinotropic polypeptide (GIP), insulin and C peptide was investigated in a placebo-controlled study in 10 healthy male volunteers. Intravenous infusion of loxiglumide (10 mg kg-1 h-1) significantly augmented integrated incremental IR-CCK levels 7.3-fold after stimulation by a standard breakfast (504 +/- 54 vs 3.665 +/- 365 pmol-1 135 min-1, P less than 0.001), as measured by a specific CCK radioimmunoassay. Basal IR-CCK concentrations were not affected by administration of loxiglumide. Oral treatment with bile acids (2 g ursodeoxycholic acid plus 2 g chenodeoxycholic acid) together with the meal abolished this augmentation, whereas high-dose substitution with pancreatic enzymes (4.2 g pancreatin) reduced elevated IR-CCK levels by only 38%. CCK-like bioactivity, determined by a bioassay using rat pancreatic acini, was not detectable in all samples that contained loxiglumide at plasma concentrations of 100-250 micrograms ml-1. Plasma gastrin concentrations in response to the breakfast were elevated 3.2-fold during loxiglumide infusion and not influenced by substitution with bile acids or pancreatic enzymes. Meal-stimulated integrated incremental plasma PP concentrations were significantly suppressed (55-65% inhibition, P less than 0.01) by loxiglumide. Infusion of the CCK receptor antagonist only slightly increased postprandial peak plasma glucose, insulin and C-peptide levels, whereas GIP and neurotensin levels were not significantly influenced. These findings suggest: (i) CCK secretion is under feedback control by intraduodenal bile acids and to a lesser extent by pancreatic enzymes; (ii) simultaneous extraction of CCK and loxiglumide results in circulating plasma CCK-like bioactivity of zero; (iii) gastrin secretion is feedback controlled via an indirect mechanism probably involving CCK-induced somatostatin secretion; (iv) release of PP is under inhibitory control of CCK; (v) CCK does not play a major role as insulinotropic hormone in the entero-insular axis in humans. SN - 0014-2972 UR - https://www.unboundmedicine.com/medline/citation/1752290/Cholecystokinin_receptor_antagonist_loxiglumide_modulates_plasma_levels_of_gastro_entero_pancreatic_hormones_in_man__Feedback_control_of_cholecystokinin_and_gastrin_secretion_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2972&date=1991&volume=21&issue=5&spage=501 DB - PRIME DP - Unbound Medicine ER -