Diazepam-binding inhibitor mediates feedback regulation of pancreatic secretion and postprandial release of cholecystokinin.
Recently, we isolated a trypsin-sensitive cholecystokinin-releasing peptide (CCK-RP) from porcine and rat intestinal mucosa. The amino acid sequence of this peptide was determined to be identical to that of the diazepam-binding inhibitor (DBI). To test the role of DBI in pancreatic secretion and responses to feeding, we used pancreaticobiliary and intestinal cannula to divert bile-pancreatic juice from anesthetized rats. Within 2 hours, this treatment caused a 2-fold increase in pancreatic protein output and a >10-fold increase in plasma CCK. Luminal DBI levels increased 4-fold. At 5 hours after diversion of bile-pancreatic juice, each of these measures returned to basal levels. Intraduodenal infusion of peptone evoked a 5-fold increase in the concentration of luminal DBI. In separate studies, we demonstrated that intraduodenal administration of antiserum to a DBI peptide specifically abolished pancreatic secretion and the increase in plasma CCK levels after diversion of bile-pancreatic juice. To demonstrate that DBI mediates the postprandial rise in plasma CCK levels, we showed that intraduodenal administration of 5% peptone induced dramatic increases in pancreatic secretion and plasma CCK, effects that could be blocked by intraduodenal administration of anti-DBI antiserum. Hence, DBI, a trypsin-sensitive CCK-RP secreted from the proximal small bowel, mediates the feedback regulation of pancreatic secretion and the postprandial release of CCK.
Li
Y
Y
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.
Hao
Y
Y
Owyang
C
C
D000214:Acyl Coenzyme A / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D026261:Diazepam Binding Inhibitor; D005246:Feedback; D006133:Growth Substances / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010179:Pancreas / Q000502:physiology*; D019518:Postprandial Period / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014359:Trypsin Inhibitor, Kazal Pancreatic
D000214:Acyl Coenzyme A; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C504705:Spink1 protein, rat; D014359:Trypsin Inhibitor, Kazal Pancreatic