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This version published online on November 5, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-1503
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Submitted on July 14, 2009
Accepted on October 9, 2009

Endogenous Glucagon-Like Peptide-1 Slows Gastric Emptying in Healthy Subjects, Attenuating Postprandial Glycemia

Adam M. Deane*, Nam Q. Nguyen, Julie E. Stevens, Robert J. L. Fraser, Richard H. Holloway, Laura K. Besanko, Carly Burgstad, Karen L. Jones, Marianne J. Chapman, Chris K. Rayner, and Michael Horowitz

Disciplines of Anaesthesia and Intensive Care (A.M.D., M.J.C.) and Medicine (J.E.S., R.J.L.F., K.L.J., C.K.R., M.H.), University of Adelaide, Adelaide, South Australia 5005 Australia; Departments of Intensive Care Medicine (A.M.D., M.J.C.) and Gastroenterology (N.Q.N., R.H.H., C.B., C.K.R.), Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia; and Investigations and Procedures Unit (R.J.L.F., L.K.B.), Repatriation General Hospital, Daw Park, South Australia 5041, Australia

* To whom correspondence should be addressed. E-mail: adam.deane{at}adelaide.edu.au.

Introduction: The role of glucagon-like peptide-1 (GLP-1) in the regulation of gastric emptying is uncertain. The aim of this study was to determine the effects of endogenous GLP-1 on gastric emptying, glucose absorption, and glycemia in health.

Methods: Ten healthy fasted subjects (eight males, two females; 48 ± 7 yr) received the specific GLP-1 antagonist, exendin(9-39) amide [ex(9-39)NH2] (300 pmol/kg · min iv), or placebo, between -30 and 180 min in a randomized, double-blind, crossover fashion. At 0 min, a mashed potato meal (~2600 kJ) containing 3 g 3-ortho-methyl-D-glucose (3-OMG) and labeled with 20 MBq 99mTechnetium-sulphur colloid was eaten. Gastric emptying, including the time taken for 50% of the meal to empty from the stomach (T50), blood glucose, plasma 3-OMG, and plasma insulin were measured.

Results: Ex(9-39)NH2 accelerated gastric emptying [T50 ex(9-39)NH2, 68 ± 8 min, vs. placebo, 83 ± 7 min; P < 0.001] and increased the overall glycemic response to the meal [area under the curve (0-180 min) ex(9-39)NH2, 1540 ± 106 mmol/liter · min, vs. placebo, 1388 ± 90 mmol/liter · min; P < 0.02]. At 60 min, ex(9-39)NH2 increased the rise in glycemia [ex(9-39)NH2, 9.9 ± 0.5 mmol/liter, vs. placebo, 8.4 ± 0.5 mmol/liter; P < 0.01], plasma 3-OMG [ex(9-39)NH2, 0.25 ± 0.01 mmol/liter, vs. placebo, 0.21 ± 0.01 mmol/liter; P < 0.05], and plasma insulin [ex(9-39)NH2, 82 ± 13 mU/liter, vs. placebo, 59 ± 9 mU/liter; P < 0.05] concentrations. There was a close within-subject correlation between glycemia and gastric emptying [e.g. at 60 min, the increment in blood glucose and gastric emptying (T50); r = -0.89; P < 0.001].

Conclusion: GLP-1 plays a physiological role to slow gastric emptying in health, which impacts on glucose absorption and, hence, postprandial glycemia.






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