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Intraduodenal administration of exogenous pancreatic secretory trypsin inhibitor\u2010I (<jats:styled-content style=\"fixed-case\">PSTI<\/jats:styled-content>\u2010I, also known as monitor peptide) causes cholecystokinin (<jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>) secretion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>We proposed that stimulation of <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> release by <jats:styled-content style=\"fixed-case\">PSTI<\/jats:styled-content> would produce gall bladder contraction and prevent gallstones in mice fed a lithogenic diet. Therefore, we tested the effect of overexpression of rat <jats:styled-content style=\"fixed-case\">PSTI<\/jats:styled-content>\u2010I in pancreatic acinar cells on plasma <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> levels and gall bladder function in a transgenic mouse line (<jats:italic>TgN[Psti1]<\/jats:italic>; known hereafter as <jats:styled-content style=\"fixed-case\">PSTI<\/jats:styled-content>\u2010I tg).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Importantly, <jats:styled-content style=\"fixed-case\">PSTI<\/jats:styled-content> tg mice had elevated fasting and fed plasma <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> levels compared to wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) mice. Only mice fed the lithogenic diet developed gallstones. Both fasting and stimulated plasma <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> levels were substantially reduced in both <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PSTI<\/jats:styled-content>\u2010I tg mice on the lithogenic diet. Moreover, despite higher <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> levels <jats:styled-content style=\"fixed-case\">PSTI<\/jats:styled-content>\u2010I tg animals developed more gallstones than <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Together with the previously observed decrease in <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>\u2010stimulated gall bladder emptying in mice fed a lithogenic diet, our findings suggest that a lithogenic diet causes gallstone formation by impaired <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> secretion in addition to reduced gall bladder sensitivity to <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12400","type":"journal-article","created":{"date-parts":[[2015,1,8]],"date-time":"2015-01-08T14:05:03Z","timestamp":1420725903000},"page":"237-246","source":"Crossref","is-referenced-by-count":11,"title":["Endogenous elevation of plasma cholecystokinin does not prevent gallstones"],"prefix":"10.1111","volume":"45","author":[{"given":"Rafiq A.","family":"Shahid","sequence":"first","affiliation":[{"name":"Department of Medicine Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Q.\u2010H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Gastroenterology and Hepatology Saint Louis University School of Medicine St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Fee","sequence":"additional","affiliation":[{"name":"Department of Medicine Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon J.","family":"McCall","sequence":"additional","affiliation":[{"name":"Department of Pathology Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle M.\u2010J.","family":"Romac","sequence":"additional","affiliation":[{"name":"Department of Medicine Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Vigna","sequence":"additional","affiliation":[{"name":"Department of Medicine Duke University Medical Center Durham NC USA"},{"name":"Department of Cell Biology Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodger A.","family":"Liddle","sequence":"additional","affiliation":[{"name":"Department of Medicine Duke University Medical Center Durham NC USA"},{"name":"Durham VA Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111809"},{"key":"e_1_2_7_3_1","first-page":"G319","article-title":"Regulation of cholecystokinin secretion by intraluminal releasing factors","volume":"269","author":"Liddle RA","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)91335-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"8956","DOI":"10.1016\/S0021-9258(18)48028-3","article-title":"Purification and sequencing of a trypsin\u2010sensitive cholecystokinin\u2010releasing peptide from rat pancreatic juice. 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