Glucagon-Like Peptide 1 Attenuates the Acceleration of Gastric Emptying Induced by Hypoglycemia in Healthy Subjects
- Mark P. Plummer1,2,3⇑,
- Karen L. Jones3,4,
- Chris E. Annink2,
- Caroline E. Cousins2,
- Juris J. Meier5,
- Marianne J. Chapman1,2,3,
- Michael Horowitz3,4 and
- Adam M. Deane1,2,3
- 1Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia
- 2Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia
- 3Centre for Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, Adelaide, Australia
- 4Discipline of Medicine, University of Adelaide, Adelaide, Australia
- 5Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
- Corresponding author: Mark P. Plummer, .
OBJECTIVE 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 99mTc-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.
Clinical trial reg. no. ACTRN12611000973910, www.anzctr.org.au.
- Received August 1, 2013.
- Accepted January 27, 2014.
- © 2014 by the American Diabetes Association.
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