Endogenous elevation of plasma cholecystokinin does not prevent gallstones.
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.
Duke Scholars
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- Trypsin Inhibitor, Kazal Pancreatic
- Rats
- Pancreas
- Organ Size
- Mice, Inbred C57BL
- Male
- Lipid Metabolism
- Intercellular Signaling Peptides and Proteins
- General Clinical Medicine
- Gallstones
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Trypsin Inhibitor, Kazal Pancreatic
- Rats
- Pancreas
- Organ Size
- Mice, Inbred C57BL
- Male
- Lipid Metabolism
- Intercellular Signaling Peptides and Proteins
- General Clinical Medicine
- Gallstones