Endogenous elevation of plasma cholecystokinin does not prevent gallstones.

Journal Article (Journal Article)

BACKGROUND: Regular gall bladder contraction reduces bile stasis and prevents gallstone formation. Intraduodenal administration of exogenous pancreatic secretory trypsin inhibitor-I (PSTI-I, also known as monitor peptide) causes cholecystokinin (CCK) secretion. DESIGN: We proposed that stimulation of CCK release by PSTI would produce gall bladder contraction and prevent gallstones in mice fed a lithogenic diet. Therefore, we tested the effect of overexpression of rat PSTI-I in pancreatic acinar cells on plasma CCK levels and gall bladder function in a transgenic mouse line (TgN[Psti1]; known hereafter as PSTI-I tg). RESULTS: Importantly, PSTI tg mice had elevated fasting and fed plasma CCK levels compared to wild-type (WT) mice. Only mice fed the lithogenic diet developed gallstones. Both fasting and stimulated plasma CCK levels were substantially reduced in both WT and PSTI-I tg mice on the lithogenic diet. Moreover, despite higher CCK levels PSTI-I tg animals developed more gallstones than WT animals. CONCLUSIONS: Together with the previously observed decrease in CCK-stimulated gall bladder emptying in mice fed a lithogenic diet, our findings suggest that a lithogenic diet causes gallstone formation by impaired CCK secretion in addition to reduced gall bladder sensitivity to CCK.

Full Text

Duke Authors

Cited Authors

  • Shahid, RA; Wang, DQ-H; Fee, BE; McCall, SJ; Romac, JM-J; Vigna, SR; Liddle, RA

Published Date

  • March 2015

Published In

Volume / Issue

  • 45 / 3

Start / End Page

  • 237 - 246

PubMed ID

  • 25641074

Pubmed Central ID

  • PMC4342269

Electronic International Standard Serial Number (EISSN)

  • 1365-2362

Digital Object Identifier (DOI)

  • 10.1111/eci.12400


  • eng

Conference Location

  • England