The gut hormone cholecystokinin (CCK) is primarily secreted from I-cells in the duodenum and proximal jejunum. CCK secretion is stimulated by food digests and inhibited by proteases from pancreatic juice. CCK regulates digestion and appetite, stimulates pancreatic growth, and participates in pancreatic carcinogenesis. The molecular mechanisms of CCK-induced effects are not fully understood. When the mechanisms are studied in animals, the surgical model of pancreatobiliary diversion (PBD) is frequently used. After animals have had PBD, their CCK secretion is no longer inhibited by pancreas-derived proteases, so circulating CCK is increased. PBD is established in rats and hamsters, but not in mice. In this study, we modified PBD procedures and established the model in the mouse. In an experiment, we performed PBD and sham operation (SO) in two groups of mice (20 mice per group). Twenty days after operation, 75% of the PBD mice and all SO mice survived. When plasma CCK was determined by radioimmunoassay, the PBD group had higher levels than the SO group (p < 0.001). To assess pancreatic growth, we determined pancreatic weight and pancreatic contents of protein and DNA. We also stained pancreatic sections by immunohistochemistry to show the proliferating cells that either expressed the proliferating cell nuclear antigen or were labeled with 5-bromo-2′-deoxyuridine. As a result, the pancreases of the PBD mice were heavier (p < 0.001) and had more protein (p < 0.001), DNA (p < 0.01), and proliferating cells (p < 0.01) than those of the SO counterparts. Thus, pancreatic growth was increased as a result of PBD-induced hypercholecystokininemia. The plasma and pancreatic data demonstrated that the PBD model was a success. This model may be used in CCK-related research. For instance, pancreatic cancer is frequently studied in transgenic mice. PBD may be combined with the cancer model to study the role of CCK in the molecular biology of pancreatic cancer.

1.
Koide
M
,
Okabayashi
Y
,
Otsuki
M
.
Role of endogenous bile on basal and postprandial CCK release in humans
.
Dig Dis Sci
.
1993
Jul
;
38
(
7
):
1284
90
.
[PubMed]
0163-2116
2.
Owyang
C
,
Louie
DS
,
Tatum
D
.
Feedback regulation of pancreatic enzyme secretion. Suppression of cholecystokinin release by trypsin
.
J Clin Invest
.
1986
Jun
;
77
(
6
):
2042
7
.
[PubMed]
0021-9738
3.
Kodama
Y
,
Zhao
CM
,
Kulseng
B
,
Chen
D
.
Eating behavior in rats subjected to vagotomy, sleeve gastrectomy, and duodenal switch
.
J Gastrointest Surg
.
2010
Oct
;
14
(
10
):
1502
10
.
[PubMed]
1091-255X
4.
Watanapa
P
,
Flaks
B
,
Oztas
H
,
Deprez
PH
,
Calam
J
,
Williamson
RC
.
Inhibitory effect of a cholecystokinin antagonist on pancreatic carcinogenesis after pancreatobiliary diversion
.
Br J Cancer
.
1993
Apr
;
67
(
4
):
663
7
.
[PubMed]
0007-0920
5.
Gasslander
T
,
Axelson
J
,
Håkanson
R
,
Ihse
I
,
Lilja
I
,
Rehfeld
JF
.
Cholecystokinin is responsible for growth of the pancreas after pancreaticobiliary diversion in rats
.
Scand J Gastroenterol
.
1990
Oct
;
25
(
10
):
1060
5
.
[PubMed]
0036-5521
6.
Axelson
J
,
Jansen
C
,
Sternby
B
,
Björkman
A
,
Rehfeld
JF
,
Ihse
I
.
Pancreatic growth after pancreatico-biliary diversion does not increase the capacity to secrete amylase
.
Eur Surg Res
.
1999
;
31
(
2
):
187
95
.
[PubMed]
0014-312X
7.
Hara
H
,
Ohyama
S
,
Hira
T
.
Luminal dietary protein, not amino acids, induces pancreatic protease via CCK in pancreaticobiliary-diverted rats
.
Am J Physiol Gastrointest Liver Physiol
.
2000
Jun
;
278
(
6
):
G937
45
.
[PubMed]
0193-1857
8.
Chu
M
,
Rehfeld
JF
,
Borch
K
.
Chronic endogenous hypercholecystokininemia promotes pancreatic carcinogenesis in the hamster
.
Carcinogenesis
.
1997
Feb
;
18
(
2
):
315
20
.
[PubMed]
0143-3334
9.
Hingorani
SR
,
Petricoin
EF
 3rd
,
Maitra
A
,
Rajapakse
V
,
King
C
,
Jacobetz
MA
, et al.
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
.
Cancer Cell
.
2003
Dec
;
4
(
6
):
437
50
.
[PubMed]
1535-6108
10.
Wang
F
,
Kumagai-Braesch
M
,
Herrington
MK
,
Larsson
J
,
Permert
J
.
Increased lipid metabolism and cell turnover of MiaPaCa2 cells induced by high-fat diet in an orthotopic system
.
Metabolism
.
2009
Aug
;
58
(
8
):
1131
6
.
[PubMed]
0026-0495
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.