CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growth
| Autor: | Stephen J. Crozier, John A. Williams, Jackie Y. Wang, Stephen I. Lentz, Stephen A. Ernst, M. Dolors Sans |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
MAPK/ERK pathway medicine.medical_specialty Physiology Blotting Western Hormones and Signaling mTORC1 Mechanistic Target of Rapamycin Complex 1 Biology Mice Physiology (medical) Casein Internal medicine medicine Animals Phosphorylation Cholecystokinin Mice Knockout Analysis of Variance Hepatology DNA synthesis Calcineurin TOR Serine-Threonine Kinases digestive oral and skin physiology Gastroenterology Proteins Organ Size Hyperplasia medicine.disease Pancreas Exocrine medicine.anatomical_structure Endocrinology Multiprotein Complexes Dietary Proteins Pancreas Proto-Oncogene Proteins c-akt Signal Transduction Transcription Factors |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 299:G1154-G1163 |
| ISSN: | 1522-1547 0193-1857 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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