CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growth

Stephen J. Crozier, M. Dolors Sans, Jackie Y. Wang, Stephen I. Lentz, Stephen A. Ernst, John A. Williams

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)G1154-G1163
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume299
Issue number5
DOIs
StatePublished - Nov 1 2010

Fingerprint

Exocrine Pancreas
Dietary Proteins
Growth
Proteins
DNA
Calcineurin
Caseins
Weights and Measures
Hypertrophy
mechanistic target of rapamycin complex 1
Sirolimus
Inbred C57BL Mouse
Cell Size
Hyperplasia
Pancreas
RNA

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Crozier, Stephen J. ; Sans, M. Dolors ; Wang, Jackie Y. ; Lentz, Stephen I. ; Ernst, Stephen A. ; Williams, John A. / CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growth. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2010 ; Vol. 299, No. 5. pp. G1154-G1163.
@article{94c894e5e3bd489f96f742c5d319c7d1,
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.",
author = "Crozier, {Stephen J.} and Sans, {M. Dolors} and Wang, {Jackie Y.} and Lentz, {Stephen I.} and Ernst, {Stephen A.} and Williams, {John A.}",
year = "2010",
month = "11",
day = "1",
doi = "10.1152/ajpgi.00445.2009",
language = "English (US)",
volume = "299",
pages = "G1154--G1163",
journal = "American Journal of Physiology",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "5",

}

CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growth. / Crozier, Stephen J.; Sans, M. Dolors; Wang, Jackie Y.; Lentz, Stephen I.; Ernst, Stephen A.; Williams, John A.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 299, No. 5, 01.11.2010, p. G1154-G1163.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growth

AU - Crozier, Stephen J.

AU - Sans, M. Dolors

AU - Wang, Jackie Y.

AU - Lentz, Stephen I.

AU - Ernst, Stephen A.

AU - Williams, John A.

PY - 2010/11/1

Y1 - 2010/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78149488752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149488752&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00445.2009

DO - 10.1152/ajpgi.00445.2009

M3 - Article

C2 - 20798356

AN - SCOPUS:78149488752

VL - 299

SP - G1154-G1163

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1849

IS - 5

ER -