Endogenous elevation of plasma cholecystokinin does not prevent gallstones

Rafiq A. Shahid, David Q.H. Wang, Brian E. Fee, Shannon J. Mccall, Joelle M.J. Romac, Steven R. Vigna, Rodger A. Liddle

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume45
Issue number3
DOIs
StatePublished - Mar 1 2015

    Fingerprint

Keywords

  • Bile salts
  • Cholesterol crystals
  • Gall bladder motility
  • Intestinal hormone
  • Lithogenic bile
  • Mucin gel

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Shahid, R. A., Wang, D. Q. H., Fee, B. E., Mccall, S. J., Romac, J. M. J., Vigna, S. R., & Liddle, R. A. (2015). Endogenous elevation of plasma cholecystokinin does not prevent gallstones. European Journal of Clinical Investigation, 45(3), 237-246. https://doi.org/10.1111/eci.12400