PMID- 18356533
OWN - NLM
STAT- MEDLINE
DCOM- 20080630
LR  - 20211203
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 294
IP  - 5
DP  - 2008 May
TI  - CCK-induced pancreatic growth is not limited by mitogenic capacity in mice.
PG  - G1148-57
LID - 10.1152/ajpgi.00426.2007 [doi]
AB  - In mice fed trypsin inhibitor (camostat) to elevate endogenous CCK, pancreatic 
      growth plateaus by 7 days. It is unknown whether this represents the maximum 
      growth capacity of the pancreas. To test the ability of CCK to drive further 
      growth, mice were fed chow containing camostat (0.1%) for 1 wk, then fed standard 
      chow for 1 wk, and finally returned to the camostat diet for a week. Pancreatic 
      mass increased to 245% of initial value (iv) following 1 wk of camostat feeding, 
      decreased to 147% iv following a 1 wk return to normal chow, and increased to 
      257% iv with subsequent camostat feeding. Camostat feeding was associated with 
      significant increases in circulating CCK and changes in pancreatic mass were 
      paralleled by changes in protein and DNA content. Moreover, regression of the 
      pancreas following camostat feeding was associated with changes in the expression 
      of the autophagosome marker LC3. Pancreatic protein synthetic rates were 130% of 
      control after 2 days on camostat but were equivalent to control after 7 days. 
      Changes in the phosphorylation of 4E-BP1 and S6, downstream effectors of 
      mammalian target of rapamycin (mTOR), paralleled changes in protein synthetic 
      rates. Cellular content of Akt, an upstream activating kinase of mTOR, decreased 
      after 7 days of camostat feeding whereas expression of the E3 ubiquitin-ligases 
      and the cell cycle inhibitor p21 increased after 2 days. These results indicate 
      that CCK-stimulated growth of the pancreas is not limited by acinar cell 
      mitogenic capacity but is due, at least in part, to inhibition of promitogenic 
      Akt signaling.
FAU - Crozier, Stephen J
AU  - Crozier SJ
AD  - Department of Molecular and Integrative Physiology, The University of Michigan 
      Medical School, Ann Arbor, MI 48109, USA. scrozier@umich.edu
FAU - Sans, Maria Dolors
AU  - Sans MD
FAU - Lang, Charles H
AU  - Lang CH
FAU - D'Alecy, Louis G
AU  - D'Alecy LG
FAU - Ernst, Stephen A
AU  - Ernst SA
FAU - Williams, John A
AU  - Williams JA
LA  - eng
GR  - DK 59578/DK/NIDDK NIH HHS/United States
GR  - F32 DK 0077423/DK/NIDDK NIH HHS/United States
GR  - GM 38032/GM/NIGMS NIH HHS/United States
GR  - P30 DK 34933/DK/NIDDK NIH HHS/United States
GR  - P60 DK 20572/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080320
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Eif4ebp1 protein, mouse)
RN  - 0 (Esters)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Guanidines)
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0FD207WKDU (camostat)
RN  - 4V7M9137X9 (Gabexate)
RN  - 9007-49-2 (DNA)
RN  - 9011-97-6 (Cholecystokinin)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Administration, Oral
MH  - Animals
MH  - Autophagy/drug effects/physiology
MH  - Carrier Proteins/metabolism
MH  - Cell Cycle Proteins
MH  - Cholecystokinin/*blood
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - DNA/analysis
MH  - Esters
MH  - Eukaryotic Initiation Factors
MH  - Gabexate/administration & dosage/*analogs & derivatives/pharmacology
MH  - Gene Expression/drug effects
MH  - Guanidines
MH  - Immunoblotting
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Microtubule-Associated Proteins/metabolism
MH  - Mitosis/*drug effects/physiology
MH  - Organ Size/drug effects
MH  - Pancreas/*drug effects/growth & development/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Biosynthesis/drug effects
MH  - Protein Kinases/metabolism
MH  - Proteins/analysis
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Ubiquitin-Protein Ligases/genetics/metabolism
EDAT- 2008/03/22 09:00
MHDA- 2008/07/01 09:00
CRDT- 2008/03/22 09:00
PHST- 2008/03/22 09:00 [pubmed]
PHST- 2008/07/01 09:00 [medline]
PHST- 2008/03/22 09:00 [entrez]
AID - 00426.2007 [pii]
AID - 10.1152/ajpgi.00426.2007 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1148-57. doi: 
      10.1152/ajpgi.00426.2007. Epub 2008 Mar 20.