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. 2009 Oct;297(4):G663-71. doi: 10.1152/ajpgi.90635.2008. Epub 2009 Aug 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsaicin / pharmacology
  • Cell Line
  • Dose-Response Relationship, Drug
  • Duodenum / drug effects*
  • Duodenum / innervation
  • Duodenum / metabolism
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism*
  • Ileum / drug effects*
  • Ileum / innervation
  • Ileum / metabolism
  • Jejunum / drug effects
  • Jejunum / metabolism
  • Male
  • Protein Hydrolysates
  • Rats
  • Rats, Sprague-Dawley
  • Sensory System Agents / pharmacology
  • Time Factors
  • Vagotomy
  • Vagus Nerve / physiology
  • Zein / pharmacology*


  • Protein Hydrolysates
  • Sensory System Agents
  • Glucagon-Like Peptide 1
  • Zein
  • Capsaicin