title: Endogenous elevation of plasma cholecystokinin does not prevent gallstones.
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.
  
  
  METHODS
  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.
authors: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors: Rafiq A
authors: RA
authors: Shahid
authors: David Q-H
authors: DQ
authors: Wang
authors: Brian E
authors: BE
authors: Fee
authors: Shannon J
authors: SJ
authors: McCall
authors: Joelle M-J
authors: JM
authors: Romac
authors: Steven R
authors: SR
authors: Vigna
authors: Rodger A
authors: RA
authors: Liddle
mesh_terms: D061354:Acinar Cells / Q000378:metabolism; D000818:Animals; D002764:Cholecystitis / Q000473:pathology; D002766:Cholecystokinin / Q000378:metabolism*; D004032:Diet; D005704:Gallbladder / Q000473:pathology; D016473:Gallbladder Emptying / Q000502:physiology; D042882:Gallstones / Q000503:physiopathology / Q000517:prevention & control*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000502:physiology; D010179:Pancreas / Q000166:cytology; D051381:Rats; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C504705:Spink1 protein, rat; D014359:Trypsin Inhibitor, Kazal Pancreatic; D002766:Cholecystokinin
keywords: Bile salts; cholesterol crystals; gall bladder motility; intestinal hormone; lithogenic bile; mucin gel
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