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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/G1148    most recent 00426.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Crozier, S. J. Articles by Williams, J. A. PubMed PubMed Citation Articles by Crozier, S. J. Articles by Williams, J. A.

HORMONES AND SIGNALING

CCK-induced pancreatic growth is not limited by mitogenic capacity in mice

¹Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor; ²Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania; and ³Department of Cell and Developmental Biology, The University of Michigan Medical School, Ann Arbor, Michigan

Submitted 20 September 2007 ; accepted in final form 18 March 2008

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.

pancreatic acinar cell; protein metabolism; cholecystokinin