Absence of a Memory Effect for the Insulinotropic Action of Glucagon-like Peptide 1 (GLP-1) in Healthy Volunteers

S. Meier; K. Hücking; R. Ritzel; J. J. Holst; W. H. Schmiegel; M. A. Nauck

doi:10.1055/s-2003-42658

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2003; 35(9): 551-556
DOI: 10.1055/s-2003-42658

Original Clinical

Absence of a Memory Effect for the Insulinotropic Action of Glucagon-like Peptide 1 (GLP-1) in Healthy Volunteers

S. Meier¹ , K. Hücking¹ , R. Ritzel¹ , J. J. Holst² , W. H. Schmiegel¹ , M. A. Nauck^1, ³

¹Medizinische Universitäts-Klinik, Knappschafts-Krankenhaus Bochum, Klinikum der Ruhr-Universität Bochum, Germany
²Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark
³Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany

Abstract

Background/Aims: The term memory effect refers to the phenomenon that B cell stimuli retain some of their insulinotropic effects after they have been removed. Memory effects exist for glucose and sulfonylureas. It is not known whether there is a B-cell memory for incretin hormones such as GLP-1. Subjects/Methods: Eight healthy young volunteers were studied on four occasions in the fasting state. In one experiment, placebo was administered (a), in three more experiments (random order), synthetic GLP-1 (7 - 36 amide) at 1.2 pmol/kg/min was administered over a period of three hours. At 0 min, a bolus of glucose was injected intravenously (0.33 g/kg body weight). GLP-1 was infused from (b) - 60 to 120 min, (c) - 210 to - 30 min, or (d) - 300 to - 120 min. Glucose (glucose oxidase), insulin, C-peptide, GLP-1, and glucagon (immunoassays) were determined. Statistical analysis was carried out by ANOVA and appropriate post hoc tests. Results: GLP-1 plasma levels during the infusion periods were elevated to 89 ± 9, 85 ± 13, and 89 ± 6 pmol/l (p < 0.0001 vs. placebo, 10 ± 1 pmol/l). Glucose was eliminated faster (p < 0.0001), with an enhanced negative rebound (p = 0.014), and insulin and C-peptide increments were greater after intravenous glucose administration (p < 0.0001) if GLP-1 was administered during the injection of the glucose bolus, but not if GLP-1 had been administered until 120 or 30 min before the glucose load. There was a trend towards higher insulin concentrations (p = 0.056) five minutes after glucose with GLP-1 administered until - 30 min before the glucose load. Glucagon was suppressed by exogenous glucose, but increased significantly (p = 0.013) during the induction of reactive hypoglycemia after glucose injection during GLP-1 administration. Conclusion: 1) No memory effect appears to exist for insulinotropic actions of GLP-1, in line with clinical data. 2) Reactive hypoglycemia causes a prompt rise in glucagon despite pharmacological circulating concentrations of GLP-1. 3) Similar studies should be performed in Type 2-diabetic patients, because exposure to GLP-1 might recruit dormant pancreatic B cells to become glucose-competent, and this might contribute to the overall antidiabetogenic effect of GLP-1 in such patients.

Key words

Incretin - Memory Effect - Priming Effect - Glucose Competence - Time-Dependent Activation

Full Text

References

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