GLP-1 secretion is enhanced directly in the ileum but indirectly in the duodenum by a newly identified potent stimulator, zein hydrolysate, in rats.
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.
Hira
Tohru
T
Division of Applied Biosciences, Research Faculty of Agriculture, Graduate School of Agriculture, Hokkaido University, Sapporo, Japan. hira@chem.agr.hokudai.ac.jp
Mochida
Taisuke
T
Miyashita
Kyoko
K
Hara
Hiroshi
H
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011492:Protein Hydrolysates; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology; D015028:Zein / Q000494:pharmacology*
D011492:Protein Hydrolysates; D018689:Sensory System Agents; D052216:Glucagon-Like Peptide 1; D015028:Zein; D002211:Capsaicin