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Effects of Intravenous Glucagon-Like Peptide-1 on Gastric Emptying and Intragastric Distribution in Healthy Subjects: Relationships with Postprandial Glycemic and Insulinemic Responses

Department of Medicine (T.J.L., A.N.P., A.R., L.P., K.L.J., J.W., M.H., C.F.-B.), University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia; and Diabeteszentrum (M.A.N.), 37431 Bad Lauterberg, Germany

Address all correspondence to: Christine Feinle-Bisset, Ph.D., National Health and Medical Research Council Senior Research Fellow, Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. E-mail: christine.feinle{at}adelaide.edu.au.

Context: The inhibitory action of glucagon-like peptide-1 (GLP-1) on gastric emptying (GE) is likely to be important in mediating its effects on postprandial glycemia, appetite, and gastrointestinal symptoms.

Objective: The objective of the study was to evaluate the effects of "low" and "high" doses of iv GLP-1 on GE, intragastric meal distribution, glycemia, insulinemia, and appetite.

Design: Ten healthy males were studied on 3 d. GE of a solid (ground beef)/liquid (glucose) meal, blood glucose, plasma insulin, glucagon and glucose-dependent insulinotropic peptide, appetite perceptions, and gastrointestinal symptoms were evaluated during iv infusion of: 1) GLP-1 at 0.3 pmol·kg^–1·min^–1 (GLP-1 0.3); 2) GLP-1 at 0.9 pmol·kg^–1·min^–1 (GLP-1 0.9); and 3) 0.9% saline.

Results: GLP-1 0.3 and 0.9 slowed GE of solid (intragastric retention at t = 100 min; saline: 28 ± 5%; GLP-1 0.3: 53 ± 6%; GLP-1 0.9: 58 ± 7%; P < 0.001) and liquid (time for 50% of the liquid to empty, saline: 28 ± 2 min; GLP-1 0.3: 42 ± 7 min; GLP-1 0.9: 50 ± 9 min; P < 0.001). Both doses of GLP-1 induced gastroparesis in about half the cohort and increased meal retention in the distal stomach (P < 0.05). GLP-1 attenuated the rises in glucose, insulin, and glucose-dependent insulinotropic peptide (P < 0.05). There was an inverse relationship between blood glucose at t = 15 min and the time for 50% of the liquid to empty (r = –0.70, P < 0.001).

Conclusions: In healthy subjects exogenous GLP-1 increases meal retention in the distal stomach and, even when administered in a "low" dose, frequently induces "gastroparesis," and the effects of GLP-1 on postprandial glycemia are predictable on the basis of its effect on GE, supporting the concept that GE is a major target mechanism for the clinical use of incretin mimetics.

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