Altered Pancreatic Protein Synthesis During Chronic CCK Stimulation

Elevated concentrations of the hormone cholecystokinin (CCK) induce pancreatic growth. In mice fed trypsin inhibitor (TI) to chronically elevate endogenous CCK, pancreatic growth plateaus by 7‐10 days at twice normal size. 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 with TI (FOY‐305, 0.1 %) for 1 week, then fed standard chow for 1 week, and finally returned to the TI diet for an additional week. Pancreatic mass increased to 225% of initial values (iv) following 1 week of TI feeding, decreased to 134% iv following a 1 week return to normal chow, and then increased to 221% iv with subsequent TI feeding. Changes in pancreatic mass were paralleled by changes in protein and DNA content. Pancreatic protein synthetic rates, measured by the 3 H‐phenylalanine flooding dose technique, were 132% of control in mice after 2 days on TI diet, the time of maximal DNA synthesis as measured by BrdU incorporation, but were equivalent to control after 7 days on TI diet when DNA synthesis had returned towards baseline, and decreased to 58% of control one day after removal of dietary TI. Changes in protein synthesis corresponded with increased phosphorylation of downstream effectors of the growth‐promoting mTOR pathway, 4E‐BP1 and S6, after 2 days of TI feeding and decreased effector phosphorylation one day after dietary TI removal. These results indicate that the pancreas has the capacity to undergo multiple rounds of CCK‐stimulated growth and is not limited by a capacity for acinar cell division. This research was supported by a grant from the NIH (JAW: DK59578).