Hira T, Mochida T, Miyashita K, Hara H. GLP-1 secretion is enhanced directly in the ileum but indirectly in the duodenum by a newly identified potent stimulator, zein hydrolysate, in rats. Am J Physiol Gastrointest Liver Physiol 297: G663-G671, 2009. First published August 6, 2009; doi:10.1152/ajpgi.90635.2008.-Glucagon-like peptide-1 (GLP-1) is released from enteroendocrine cells (L cells) in response to food ingestion. The mechanism by which dietary peptides stimulate GLP-1 secretion in the gut is unknown. In the present study, we found that a hydrolysate prepared from zein, a major corn protein [zein hydrolysate (ZeinH)], strongly stimulates GLP-1 secretion in enteroendocrine GLUTag cells. Stimulatory mechanisms of GLP-1 secretion induced by ZeinH were investigated in the rat small intestine under anesthesia. Blood was collected through a portal catheter before and after ZeinH administration into different sites of the small intestine. The duodenal, jejunal, and ileal administration of ZeinH induced dose-dependent increases in portal GLP-1 concentration. GLP-1 secretion in response to the ileal administration of ZeinH was higher than that in the duodenal or jejunal administration. Capsaicin treatment on esophageal vagal trunks abolished the GLP-1 secretion induced by duodenal ZeinH but did not affect the secretion induced by jejunal or ileal ZeinH. These results suggest that ZeinH in the jejunum or ileum directly stimulates GLP-1 secretion but duodenal ZeinH indirectly stimulates GLP-1 secretion via the vagal afferent nerve. A direct blood sampling method from the duodenal vein and ileal mesenteric vein revealed that ZeinH administered into the ligated duodenal loop enhanced GLP-1 concentration in the ileal mesenteric vein but not in the duodenal vein. This confirmed that ZeinH in the duodenum induces GLP-1 secretion from L cells located in the ileum by an indirect mechanism. These results indicate that a potent GLP-1-releasing peptide, ZeinH, induces GLP-1 secretion by direct and indirect mechanisms in the rat intestine.glucagon-like peptide-1; GLUTag cells; dietary peptide; zein GLUCAGON-LIKE PEPTIDE-1 (GLP-1) is one of the incretin hormones that stimulate glucose-dependent insulin secretion and pancreatic ␤-cell proliferation (4, 9); GLP-1 also inhibits gastric emptying and food intake. In addition, a recent study demonstrated that GLP-1 reduces lipid absorption in rats (27). These actions of GLP-1 could present great benefits for the treatment of type-II diabetes mellitus. Stable GLP-1 analogs and dipeptidyl peptidase-IV (DPP-IV) inhibitors that protect active GLP-1 from cleavage by DPP-IV have been developed for clinical use (10).Glucose and fatty acids are potent stimulants of GLP-1 release from enteroendocrine L cells in the distal intestine in response to food ingestion (1,14). Previous studies have demonstrated that fatty acids stimulate GLP-1 secretion via direct and indirect mechanisms (30,31,32). At the cellular level, studies using murine GLP-1-producing enteroendocrine cell lines show that sodiu...

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