title: CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growth.
abstract: Dietary protein can stimulate pancreatic growth in the absence of CCK release, but there is little data on the regulation of CCK-independent growth. To identify mechanisms whereby protein stimulates pancreatic growth in the absence of CCK release, C57BL/6 control and CCK-null male mice were fed normal-protein (14% casein) or high-protein (75% casein) chow for 7 days. The weight of the pancreas increased by 32% in C57BL/6 mice and 26% in CCK-null mice fed high-protein chow. Changes in pancreatic weight in control mice were due to both cell hypertrophy and hyperplasia since there was an increase in protein-to-DNA ratio, total DNA content, and DNA synthesis. In CCK-null mice pancreatic growth was almost entirely due to hypertrophy with both protein-to-DNA ratio and cell size increasing without significant increases in DNA content or DNA synthesis. ERK, calcineurin, and mammalian target of rapamycin complex 1 (mTORC1) are activated in models of CCK-induced growth, but there were no differences in ERK or calcineurin activation between fasted and fed CCK-null mice. In contrast, mTORC1 activation was increased after feeding and the duration of activation was prolonged in mice fed high-protein chow compared with normal-protein chow. Changes in pancreatic weight and RNA content were completely inhibited, and changes in protein content were partially abated, when the mTORC1 inhibitor rapamycin was administered during high-protein chow feeding. Prolonged mTORC1 activation is thus required for dietary protein-induced pancreatic growth in the absence of CCK.
authors.affiliation: Department of 1Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Crozier
authors.forename: M Dolors
authors.initials: MD
authors.lastname: Sans
authors.forename: Jackie Y
authors.initials: JY
authors.lastname: Wang
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Lentz
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ernst
authors.forename: John A
authors.initials: JA
authors.lastname: Williams
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D004044:Dietary Proteins / Q000378:metabolism*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D009929:Organ Size; D046790:Pancreas, Exocrine / Q000254:growth & development* / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004044:Dietary Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D002766:Cholecystokinin; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D019703:Calcineurin
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