Jejunal bypass stimulation of pancreatic growth and cholecystokinin secretion in rats: importance of luminal nutrients.

Abstract

SUMMARYThe effect of jejunal bypass on pancreatic growth and plasma cholecystokinin (CCK) was investigated in rats. Rats underwent bypass of jejunum or sham operation. Rats with jejunal bypass were further divided into three groups; one group received a continuous infusion of a partially hydrolysed liquid diet (Vital) into the bypassed jejunum; a second group received the nutrient solution mixed with trypsin and infused into the bypassed jejunum; the third bypass group did not receive infusion of nutrient or trypsin into the jejunum. Jejunal bypass alone did not significantly stimulate pancreatic growth or DNA content at one or two weeks postoperative. Infusion of nutrient solution into the bypassed jejunum stimulated pancreatic growth and DNA content, with maximal increases of 185 % and 181 % for pancreatic weight and DNA content, respectively, at two weeks. This coincided with significant increases in postabsorptive plasma CCK concentrations. Infusion of pancreatic proteases into the bypassed jejunum partially reversed the effects of nutrient infusion. These results suggest that exclusion of bile-pancreatic juice or pancreatic proteases from the jejunum does not lead to maximal release of CCK unless the jejunum receives luminal nutrients. It is proposed that CCK release from rat jejunum occurs spontaneously in the absence of pancreatic proteases, and that luminal nutrients in bypassed jejunum increase plasma CCK and stimulate pancreatic growth by maintaining synthesis of CCK.Exclusion of bile-pancreatic juice (BPJ) from the proximal small intestine stimulates pancreatic secretion and growth,' and increases plasma cholecystokinin (CCK) in the rat.23 These phenomena are attributed to loss of feedback inhibition of CCK release by luminal pancreatic proteases.45 Transposition of the duodenum to lie between the jejunum and ileum also stimulates pancreatic growth in the rat.6 We suggested that this was caused by the consequent diversion of BPJ from the jejunum to the ileum, resulting in loss of protease induced inhibition of CCK release from the jejunum.I The results of this latter study6 indicated that the jejunum may be the major site of feedback control of CCK release in the proximal small intestine in the rat, because in that model BPJ was diverted from the jejunum, but not

Peptone stimulates CCK-releasing peptide secretion by activating intestinal submucosal cholinergic neurons.

“…Similar to the observations of Spannagel and Green (23), and Levan et al (24), we found that peptone could stimulate CCK secretion in rats with diversion of bile pancreatic juice. Peptides appear to mediate the effect of peptone because mixed amino acids were ineffective to evoke pancreatic secretion or plasma CCK release.…”

“…Peptides appear to mediate the effect of peptone because mixed amino acids were ineffective to evoke pancreatic secretion or plasma CCK release. It has been proposed that luminal nutrients may be necessary to maintain normal CCK synthetic activity and that the release of CCK occurs spontaneously in the absence of the suppressive effects of pancreatic proteases (24). Our studies clearly demonstrate that peptone in the duodenum acts by stimulating the luminal secretion of CCK-RP and this in turn stimulates the release of CCK.…”

Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK.

“…In the rat it has been well demonstrated that diversion of pancreatico-biliary juice from the duodenum, or inhibition of duodenal pancreatic enzyme activity with trypsin inhibitors, causes a prompt increase in pancreatic exocrine secretion (17). It has recently been confirmed that CCK is stimulated both by pancreatic diversion and trypsin inhibitor ingestion, and CCK appears to mediate the negative feedback regulation of pancreatic secretion (18,19). In other species such as the dog it has been extremely difficult to demonstrate feedback regulation, and in humans the existence of similar negative feedback regulation has been debated (20-22).…”

Rapid adaptation of pancreatic exocrine function to short-term alcohol feeding in rats

“…Since these experiments were done using CCK-8, the role of CCK-58 remains unknown [50,51]. However, similar findings were ob-served during pancreatic juice diversion [52], which releases endogenous CCK [53,54] that is presumably the natural form. CCK-mediated pancreatic secretion is potently inhibited by PYY only when the AP is intact, thus requiring a vagal-vagal pathway [47].…”