DIFFERENTIAL-EFFECTS OF SUBCUTANEOUS GLP-1 ON GASTRIC-EMPTYING, ANTRODUODENAL MOTILITY, AND PANCREATIC FUNCTION IN MEN

In this study of eight healthy male volunteers, we investigated the ef fects of graded doses of subcutaneous glucagon like peptide-1(7-36)ami de (GLP-1) on: 1) the gastric emptying pattern of a mixed liquid meal (300 kcal): 2) pancreatic enzyme secretion; 3) antroduodenal motility; and 4) the glycemic response as well as releases of subcutaneously 5 min before meal ingestion. Subcutaneous GLP-1 dose-dependently prolong ed the lag period (i.e., the time to reach maximal velocity of gastric emptying) by 46.2% (low dose) and 93.7% (high dose) (p < .05) but lef t unaltered maximal emptying velocity, total emptying time, and expone ntial emptying rate. With and without GLP-1, a fed motor pattern was i nduced by the meal and was terminated by an antral phase III when 98% of the meal had emptied. In parallel to the prolonged lag period, GLP- 1 dose-dependently inhibited antral and duodenal motility and coordina ted antroduodenal contractions by > 50% (low dose) and > 70% (high dos e) (p < .05). GLP-1 initially reduced and thereafter transiently stimu lated pancreatic enzyme secretion. This pattern correlated with the pr olonged lag period and mirrored the delayed gastric emptying. GLP-1 re tarded and diminished the postprandial glucose peak and reduced the to tal plasma glucose response by 46.6% (low dose) and by 59.4% (high dos e) (p < .05). Both doses of GLP-1 delayed the postprandial insulin pea k, enhanced total insulin release, and diminished postprandial respons es of glucagon and pancreatic polypeptide. The duration of the lag per iod strongly correlated with the timing of postprandial glucose and in sulin peaks (p < .001). The initial delay of gastric emptying, the enh ancement of postprandial insulin release, and the inhibition of postpr andial glucagon release were independent determinants (p < .01-.05) of the postprandial glucose response after subcutaneous administration o f GLP-1.