ILEAL RELEASE OF GLUCAGON-LIKE PEPTIDE-1 (GLP-1) - ASSOCIATION WITH INHIBITION OF GASTRIC-ACID SECRETION IN HUMANS

There is evidence that the distal intestine participates in the regula tion of gastric motor and secretory function. It was the aim of this s tudy to examine in greater detail the effects of ileal nutrient exposu re on human gastric acid secretion and to investigate potential interm ediary mechanisms. Twelve normal subjects were intubated with an oroil eal multilumen tube assembly for gastric, duodenal, and ileal perfusio n of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, i nterdigestive state (during early phase II, N = 6), and during endogen ous stimulation by intraduodenal essential amino acid perfusion, N = 6 ) and on release of candidate humoral mediators, peptide YY (PW) and g lucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydra te (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P < 0.01), and endogenously stimulated output by 68%, respectively (P < 0.005). Under all experimental conditions, ileal car bohydrate increased plasma GLP-1 by 80-100% (all P < 0.005). Ileal lip id perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By co ntrast, ileal perfusion with peptone had no or only weak effects on ei ther acid output or plasma GLP-1. Plasma PW concentrations and suppres sion of gastric secretion in response to ileal perfusions were not cor related. In humans, both interdigestive and endogenously stimulated ga stric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein, Decreased acid output is associated with release of GLP-1, but not PYY. These findings support the hypothesis t hat the distal small intestine may participate in the late postprandia l inhibitory regulation of gastric secretory function in humans and th at GLP-1 may be an intermediary factor.