Endogenous elevation of plasma cholecystokinin does not prevent gallstones

Rafiq A. Shahid, David Q.H. Wang, Brian E. Fee, Shannon J. Mccall, Joelle M J Romac, Steven R. Vigna, Rodger A. Liddle

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume45
Issue number3
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Cholecystokinin
Gallstones
Plasmas
Nutrition
Diet
Urinary Bladder
Fasting
Animals
Kazal Pancreatic Trypsin Inhibitor
Gallbladder Emptying
Wild Animals
Acinar Cells
Bile
Transgenic Mice
Rats
Peptides

Keywords

  • Bile salts
  • Cholesterol crystals
  • Gall bladder motility
  • Intestinal hormone
  • Lithogenic bile
  • Mucin gel

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry
  • Clinical Biochemistry

Cite this

Shahid, R. A., Wang, D. Q. H., Fee, B. E., Mccall, S. J., Romac, J. M. J., Vigna, S. R., & Liddle, R. A. (2015). Endogenous elevation of plasma cholecystokinin does not prevent gallstones. European Journal of Clinical Investigation, 45(3), 237-246. https://doi.org/10.1111/eci.12400

Endogenous elevation of plasma cholecystokinin does not prevent gallstones. / Shahid, Rafiq A.; Wang, David Q.H.; Fee, Brian E.; Mccall, Shannon J.; Romac, Joelle M J; Vigna, Steven R.; Liddle, Rodger A.

In: European Journal of Clinical Investigation, Vol. 45, No. 3, 01.01.2015, p. 237-246.

Research output: Contribution to journalArticle

Shahid, RA, Wang, DQH, Fee, BE, Mccall, SJ, Romac, JMJ, Vigna, SR & Liddle, RA 2015, 'Endogenous elevation of plasma cholecystokinin does not prevent gallstones', European Journal of Clinical Investigation, vol. 45, no. 3, pp. 237-246. https://doi.org/10.1111/eci.12400
Shahid, Rafiq A. ; Wang, David Q.H. ; Fee, Brian E. ; Mccall, Shannon J. ; Romac, Joelle M J ; Vigna, Steven R. ; Liddle, Rodger A. / Endogenous elevation of plasma cholecystokinin does not prevent gallstones. In: European Journal of Clinical Investigation. 2015 ; Vol. 45, No. 3. pp. 237-246.
@article{7bfc3db50abd4552a331cee3fd13003c,
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. 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.",
keywords = "Bile salts, Cholesterol crystals, Gall bladder motility, Intestinal hormone, Lithogenic bile, Mucin gel",
author = "Shahid, {Rafiq A.} and Wang, {David Q.H.} and Fee, {Brian E.} and Mccall, {Shannon J.} and Romac, {Joelle M J} and Vigna, {Steven R.} and Liddle, {Rodger A.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1111/eci.12400",
language = "English (US)",
volume = "45",
pages = "237--246",
journal = "European Journal of Clinical Investigation",
issn = "0014-2972",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Endogenous elevation of plasma cholecystokinin does not prevent gallstones

AU - Shahid, Rafiq A.

AU - Wang, David Q.H.

AU - Fee, Brian E.

AU - Mccall, Shannon J.

AU - Romac, Joelle M J

AU - Vigna, Steven R.

AU - Liddle, Rodger A.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Bile salts

KW - Cholesterol crystals

KW - Gall bladder motility

KW - Intestinal hormone

KW - Lithogenic bile

KW - Mucin gel

UR - http://www.scopus.com/inward/record.url?scp=84923312133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923312133&partnerID=8YFLogxK

U2 - 10.1111/eci.12400

DO - 10.1111/eci.12400

M3 - Article

C2 - 25641074

AN - SCOPUS:84923312133

VL - 45

SP - 237

EP - 246

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

SN - 0014-2972

IS - 3

ER -