GLUCAGON-LIKE PEPTIDE-1 AND GLUCOSE-DEPENDENT INSULIN-RELEASING POLYPEPTIDE PLASMA-LEVELS IN RESPONSE TO NUTRIENTS

The nutrient-dependent glucagon-like peptide-1 (7-36) amide (GLP-1) re lease was studied in comparison to the glucose-dependent insulin-relea sing polypeptide (GIP) response in 10 healthy volunteers each undergoi ng various protocols. Plasma samples were saved up to 120 min after ch allenges by oral, intravenous or intraduodenal administration of nutri ents. Basal plasma-GLP-1 concentrations ranged between 0.4 and 1.4 pM, maximal postprandial GLP-1 levels peaked between 10 and 12 pM. Intrav enous glucose (25 g i.v.) did not change basal GLP-1 levels. Oral admi nistration of glucose (50 g) induced a biphasic GLP-1 release peaking at 30-60 min and a biphasic GIP release peaking at 5 and 45 min. This increase paralleled the secretion of insulin. Oral galactose (100 g) a nd amino acids (25 g) also induced a rapid plasma GLP-1 response. Afte r fat (67 g corn oil) a strong and long-lasting (> 120 min) increase o f GLP-1 plasma levels occurred. When a mixed liquid meal was given (6 g soybean oil, 5 g casein, 13 g glucose) immunoreactive (IR)-GLP-1 rap idly increased and peaked after 5 min with declining levels after 30 m in. In response to an intraduodenal infusion of a small glucose load ( 5.34 g within 120 min) a rapid, short-lasting GLP-1 response occurred whereas plasma GIP and insulin levels remained unaltered. Luminal perf usion of an isolated vascularly perfused rat ileum with a polydiet ind uced a rapid rise of portally released IR-GLP-1 which was followed by a sustained release. Glucose evoked sodium-dependently a sharp increas e of IR-GLP-1 levels followed by a plateau release. The intraluminal i nfusion of a mixture of amino acids or fat was without any effect on I R-GLP-1. We hypothesize that in contrast to GIP the GLP-1 release from L cells is triggered by nervous reflexes, by putative humoral factor( s) being released from the upper small intestine in addition to nutrie nt stimuli acting at the luminal surface of the gut.