Glucagon-like peptide 1 attenuates the acceleration of gastric emptying induced by hypoglycemia in healthy subjects

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dc.contributor.authorPlummer, M.
dc.contributor.authorJones, K.
dc.contributor.authorAnnink, C.
dc.contributor.authorCousins, C.
dc.contributor.authorMeier, J.
dc.contributor.authorChapman, M.
dc.contributor.authorHorowitz, M.
dc.contributor.authorDeane, A.
dc.date.issued2014
dc.description.abstractOBJECTIVE: Exogenous GLP-1 slows gastric emptying in health and diabetes leading to diminished glycemic excursions. Gastric emptying is markedly accelerated by hypoglycemia. The primary objective was to determine whether GLP-1 attenuates the acceleration of gastric emptying induced by hypoglycemia. RESEARCH DESIGN AND METHODS: Ten healthy volunteers were studied on four separate days in a randomized double-blind fashion. Blood glucose was stabilized using a glucose/insulin clamp at hypoglycemia (2.6 mmol/L on two occasions [hypo]) or euglycemia (6.0 mmol/L on two occasions [eu]) between T = -15 and 45 min before clamping at 6.0 mmol/L until 180 min. During hypoglycemia and euglycemia, subjects received intravenous GLP-1 (1.2 pmol/kg/min) or placebo. At T = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq (99m)Tc-sulfur-colloid and 3 g of 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from T = 0 to 180 min and serum 3-OMG taken at 15-min intervals. The areas under the curve for gastric emptying and 3-OMG concentration were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests. RESULTS: Gastric emptying was accelerated during hypoglycemia (hypo/placebo vs. eu/placebo; P < 0.001), as was glucose absorption (P < 0.03). GLP-1 slowed emptying during euglycemia (eu/placebo vs. eu/GLP-1; P < 0.001). However, hypoglycemia-induced acceleration of gastric emptying on placebo was markedly diminished by GLP-1 (hypo/placebo vs. hypo/GLP-1; P < 0.008), as was glucose absorption (P < 0.01). CONCLUSIONS: Acute administration of exogenous GLP-1 attenuates, but does not abolish, the acceleration of gastric emptying by insulin-induced hypoglycemia in healthy subjects.
dc.description.statementofresponsibilityMark P. Plummer, Karen L. Jones, Chris E. Annink, Caroline E. Cousins, Juris J. Meier, Marianne J. Chapman, Michael Horowitz and Adam M. Deane
dc.identifier.citationDiabetes Care, 2014; 37(6):1509-1515
dc.identifier.doi10.2337/dc13-1813
dc.identifier.issn0149-5992
dc.identifier.issn1935-5548
dc.identifier.orcidPlummer, M. [0000-0002-9640-1911]
dc.identifier.orcidJones, K. [0000-0002-1155-5816]
dc.identifier.orcidChapman, M. [0000-0003-0710-3283]
dc.identifier.orcidHorowitz, M. [0000-0002-0942-0306]
dc.identifier.orcidDeane, A. [0000-0002-7620-5577]
dc.identifier.urihttp://hdl.handle.net/2440/87422
dc.language.isoen
dc.publisherAmerican Diabetes Association
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1025648
dc.rights© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
dc.source.urihttps://doi.org/10.2337/dc13-1813
dc.subjectHumans
dc.subjectHypoglycemia
dc.subjectInsulin
dc.subjectBlood Glucose
dc.subjectHypoglycemic Agents
dc.subjectGlucose Clamp Technique
dc.subjectInjections, Intravenous
dc.subjectDouble-Blind Method
dc.subjectGastric Emptying
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGlucagon-Like Peptide 1
dc.subjectIncretins
dc.subjectHealthy Volunteers
dc.titleGlucagon-like peptide 1 attenuates the acceleration of gastric emptying induced by hypoglycemia in healthy subjects
dc.typeJournal article
pubs.publication-statusPublished

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