Hormonal regulation of the 'Ileal Brake' in human

Ileal nutrients inhibit upper gastrointestinal transit and gastropancreatic secretion. This 'ileal brake' is a feedback mechanism controlling meal transit and digestion. The gut hormones GLP-1 and PYY mainly originating from the lower small intestinal L-cells are postprandially released. Still, the importance of the predominant presence of L-cells within the lower gut is obscure. Since the synthetic peptides inhibit gastropancreatic secretions, they are candidate humoral mediators of the ileal brake. Accordingly, we examined the effects of ileal nutrients on pancreatic enzyme and gastric acid secretions employing the specific GLP-1 receptor antagonist exendin(9–39) (Ex-9).

Methods: In 12 healthy volunteers, an amino acid solution (3ml/min, 0.6kcal/min) was continuously perfused into the duodenum stimulating pancreatic enzyme and gastric acid secretion. After 40min, a meal (90ml, 44kcal, starch, maltose, sodium oleate, lipid) was perfused for 15min into the ileum approximating the amount of physiologically unabsorbed nutrients. Gastroduodenal secretions were sampled in 10-min intervals during 420min and quantified using a double-marker dilution technique. On 2 days in random order, Ex-9 (300pmol·kg^-1·min^-1) or saline were IV infused.

Results: Duodenal amino acids significantly increased the output of gastric acid and pancreatic enzymes on both study days (p<0.05). Ileal nutrients reduced gastropancreatic secretion for at least 90min, and in parallel raised plasma GLP-1 and PYY. IV Ex-9 markedly suppressed the ileal brake. It raised plasma PYY (AUC 360±53 vs. 207±45 pg/ml/90min, p=0.003).

mean±SEM. *: P<0.05 vs. saline IV	Saline IV		Ex-9 IV
		% reduction		% reduction
Gastric acid (mmol/90min)	-17.7±1.9	-61.7±3.5	-11.9±2.7*	-31.6±5.1*
Trypsin (kU/90min)	-10.9±2.5	-65.4±6.9	-5.4±1.6*	-30.2±7.8*
Amylase (kU/90min)	-27.7±7.2	-38.4±7.0	-1.2±7.1*	-2.7±10.2*

Conclusions: GLP-1 mediates the 'ileal brake', the inhibition of gastropancreatic secretion induced by nutrients within the ileum. The contribution of GLP-1 to the 'ileal brake' is independent of PYY. As the GLP-1 receptor antagonist markedly enhanced PYY, we suggest a feedback inhibition of the L-cell by GLP-1. We conclude that GLP-1 plays an important role as an enterogastrone.

(supported by the DFG)