LUMINAL GLUCAGON-LIKE PEPTIDE-1(7-36) AMIDE-RELEASING FACTORS IN THE ISOLATED VASCULARLY PERFUSED RAT COLON

Glucagon-like peptide-1 (GLP-1) is released from endocrine cells of th e distal part of the gut after ingestion of a meal. GLP-1 secretion is , in part, under the control of hormonal and/or neural mechanisms. How ever, stimulation of the colonic L cells may also occur directly by th e luminal contents. This was examined in the present study, using an i solated vascularly perfused rat colon. GLP-1 immunoreactivity was meas ured in the portal effluent after luminal infusion. of a variety of co mpounds which are found in colonic contents (nutrients, fibers, bile a cids, short-chain fatty acids (SCFAs)). Oleic acid (100 mM) or a mixtu re of amino acids (total concentration 250 mM), or starch (0.5%, w/v) did not increase GLP-1 secretion over basal value. A pharmacological c oncentration of glucose (250 mM) elicited a marked release of GLP-1 wh ich was maximal at the end of infusion (400% of basal), while 5 mM glu cose was without effect on secretion. Pectin evoked a dose-dependent r elease of GLP-1 over the range 0.1-0.5% (w/v) with a maximal response at 360% of basal when 0.5% pectin was infused. Cellulose or gum arabic (0.5%) did not modify GLP-1 secretion. The SCFAs acetate, propionate or butyrate (5, 20 and 100 mM) did not induce a significant release of GLP-1. Among the four bile acids tested, namely taurocholate, cholate , deoxycholate and hyodeoxycholate, the last one was the most potent a t eliciting a GLP-1 response with a maximal release at 300% and 400% o f the basal value when 2 and 20 mM bile acid were administered respect ively. In conclusion, some fibres and bile acids are capable of releas ing colonic GLP-1 in rats and may contribute to the secretory activity of colonic L cells.