RAPID OSCILLATIONS IN PLASMA GLUCAGON-LIKE PEPTIDE-1 (GLP-1) IN HUMANS - CHOLINERGIC CONTROL OF GLP-1 SECRETION VIA MUSCARINIC RECEPTORS

The mechanisms involved in the rapid glucagon-like peptide-1 (GLP-1) r elease following glucose ingestion are poorly defined. Besides a direc t intestinal stimulation oft cells, humoral and neuronal mechanisms ha ve been discussed. We investigated the temporal pattern of GLP-1 relea se in five healthy men (aged 27.8 +/- 3.6 yr; body mass index, 23.4 +/ - 1.2 kg/m(2)) after an overnight fast for 60 min under basal conditio ns and for 60 min after an oral glucose load(OGL; 100 g) in both the p resence and absence of atropine (80 ng/kg . min, iv). Blood was sample d every 2 min, and data were evaluated for the temporal pattern of GLP -1 secretion by several computer-assisted programs (deconvolution, Pul sar analysis, and Fourier transformation). With all methods a pulsatil e pattern of plasma GLP-1 levels with a frequency of five to seven per h was detected; this remained unchanged in the different metabolic st ates and during atropine treatment. Glucose and GLP-1 plasma levels sh owed a parallel increase after OGL (OGL without atropine = control: 8. 4 +/- 2.9 and 7.9 +/- 3.0 min, respectively). Atropine infusion delaye d this increase significantly (16.8 +/- 8.07 and 17.4 +/- 6.61 min, re spectively; P < 0.02). In contrast to plasma glucose concentrations (8 2.7 +/- 0.3% of control; P < 0.05), atropine infusion reduced the inte grated 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 pla sma concentrations increase after OGL due to augmented GLP-1 pulse amp litudes but not frequency. The differential effect of atropine on gluc ose and GLP-1 plasma levels suggest a direct cholinergic muscarinic co ntrol oft cells.