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Rapid Oscillations in Plasma Glucagon-Like Peptide-1 (GLP-1) in Humans: Cholinergic Control of GLP-1 Secretion via Muscarinic Receptors¹

Zentrum Innere Medizin, Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany; and Institute of Medical Physiology C, The Panum Institute, University of Copenhagen (J.J.H.), Copenhagen, Denmark

Address all correspondence and requests for reprints to: H. J. Balks, M.D., Department of Internal Medicine, Division of Clinical Endocrinology, Medizinische Hochschule Hannover, Konstanty-Gutschow-Strasse 8, D-30623 Hannover, Germany. E-mail: 106161.3402{at}compuserve.com

The mechanisms involved in the rapid glucagon-like peptide-1 (GLP-1) release following glucose ingestion are poorly defined. Besides a direct intestinal stimulation of L cells, humoral and neuronal mechanisms have been discussed. We investigated the temporal pattern of GLP-1 release in five healthy men (aged 27.8 ± 3.6 yr; body mass index, 23.4 ± 1.2 kg/m²) after an overnight fast for 60 min under basal conditions and for 60 min after an oral glucose load (OGL; 100 g) in both the presence and absence of atropine (80 ng/kg·min, iv). Blood was sampled every 2 min, and data were evaluated for the temporal pattern of GLP-1 secretion by several computer-assisted programs (deconvolution, Pulsar analysis, and Fourier transformation). With all methods a pulsatile pattern of plasma GLP-1 levels with a frequency of five to seven per h was detected; this remained unchanged in the different metabolic states and during atropine treatment. Glucose and GLP-1 plasma levels showed a parallel increase after OGL (OGL without atropine = control: 8.4 ± 2.9 and 7.9 ± 3.0 min, respectively). Atropine infusion delayed this increase significantly (16.8 ± 8.07 and 17.4 ± 6.61 min, respectively; P < 0.02). In contrast to plasma glucose concentrations (82.7 ± 0.3% of control; P < 0.05), atropine infusion reduced the integrated GLP-1 pulse amplitude to 56.0 ± 11.3% of the control levels (P < 0.05).

In conclusion, GLP-1 is secreted in a pulsatile manner with a frequency comparable to that of pancreatic hormones. Mean GLP-1 plasma concentrations increase after OGL due to augmented GLP-1 pulse amplitudes but not frequency. The differential effect of atropine on glucose and GLP-1 plasma levels suggest a direct cholinergic muscarinic control of L cells.

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