Endogenous elevation of plasma cholecystokinin does not prevent gallstones. (March 2015)

• Record Type: Journal Article
• Authors: Shahid, Rafiq A.; Wang, David Q.‐H.; Fee, Brian E.; McCall, Shannon J.; Romac, Joelle M.‐J.; Vigna, Steven R.; Liddle, Rodger A.
• Is Part Of: European journal of clinical investigation. Volume 45:Number 3(2015:Mar.)
• Page Start: 237
• Page End: 246
• Publication Date: 2015-03
• Subjects: Pathology -- Periodicals; Medical research -- Periodicals; 616.075
• DOI: 10.1111/eci.12400
• Languages: English
• ISSNs: 0014-2972

Abstract

<abstract abstract-type="main" id="eci12400-abs-0001"> <title>Abstract</title> <sec id="eci12400-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="eci12400-sec-0002" sec-type="section"> <title>Design</title> <p>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 (<italic>TgN[Psti1]</italic>; known hereafter as PSTI‐I tg).</p> </sec> <sec id="eci12400-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="eci12400-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>