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 language | English (US) |
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Pages (from-to) | 237-246 |
Number of pages | 10 |
Journal | European Journal of Clinical Investigation |
Volume | 45 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2015 |
Externally published | Yes |
Keywords
- Bile salts
- Cholesterol crystals
- Gall bladder motility
- Intestinal hormone
- Lithogenic bile
- Mucin gel
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry