Molecular Mechanisms of Pancreatic Dysfunction Induced by Protein Malnutrition

Crozier, Stephen J.; DʼAlecy, Louis G.; Ernst, Stephen A.; Ginsburg, Lauren; Williams, John A.

doi:10.1053/j.gastro.2009.04.058

Cited by 30 publications

(36 citation statements)

References 36 publications

(41 reference statements)

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“…Moreover, protein restriction inhibited the response of acinar cells to cholecystokinin (Prost and Belleville, 1991), which plays a role in stimulating enzyme secretion in the pancreas. A similar response was observed in mice that were fed a protein-restricted diet for 4 d, and a decrease in pancreas weight and pancreatic cell atrophy was observed under these conditions (Crozier et al, 2009). Although chickens of both ages showed a decrease in pancreas weight, there was a larger reduction in younger animals -approximately 50% compared with 22% in older animals -thus contributing to the large difference in pancreatic enzymes between age groups.…”

Section: Discussionsupporting

confidence: 48%

“…In their study, Crozier et al (2009) verified that after 4 d of receiving a normoproteic diet, protein-restricted mice showed a reversal of the decreased concentration of amylase and chymotrypsin. The restoration of enzyme activity could occur because pancreatic cell death did not occur after feed restriction, and instead, only cell atrophy or a decrease in protein synthesis in the pancreas occurred (Sans et al, 2004).…”

Section: Discussionmentioning

confidence: 98%

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Digestive Enzymatic Responses of Chickens Feed-restricted and Refed as Affected by Age

2014

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The effect of feed restriction and refeeding on enzymatic activity and gastrointestinal organ weight was evaluated in chickens at two ages, 7 and 35 d of age. At each age, the birds were 70% feed-restricted for 7 d (30% of ad libitum intake) followed by ad libitum refeeding for 3 d. The control groups were fed ad libitum during equivalent periods (10 d). Pancreatic activity of chymotrypsin, trypsin, amylase and lipase, and intestinal activity of sucrase and maltase were analyzed, and the weights of the proventriculus, gizzard, pancreas, small and large intestine were obtained. Trypsin and amylase activity were lower in the feed-restricted group than in the control groups at d14, whereas sucrase activity was lower in the feed-restricted group than in the control group at d42, showing that the effect of feed restriction on enzyme activity was age-dependent. Feed restriction decreased the weight of all organs in the starter and finisher periods. Upon refeeding, the organ weight increased and reached that of the control group only in chickens that were feed-restricted from d35 to d42. In the starter period, proventriculus and gizzard were less affected by feed restriction. In the finisher period, the gizzard was also the least affected organ, while the small intestine was the most affected. All effects of feed restriction were reversed after 3 days of ad libitum refeeding, indicating that the alterations were fast and reversible. Moreover, response to feed restriction and refeeding is age dependent.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 98%

Digestive Enzymatic Responses of Chickens Feed-restricted and Refed as Affected by Age

2014

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“…modulation of protein and rRNA synthesis (23,26,37). However, much of the protein content of pancreatic acinar cells consists of digestive enzyme zymogens, and prior results from our laboratory indicate that the mTORC1 pathway does not directly regulate the synthesis of these enzymes (6). Therefore, Western blotting was performed on pancreas samples from postabsorptive mice (i.e., collected at 9 AM without prior fasting or refeeding so as to minimize potential changes in digestive enzyme content resulting from secretion) to elucidate whether rapamycin-induced decreases in pancreatic weight are associated with decreased pancreatic digestive enzyme content.…”

Section: Feeding a Protein-enriched Diet Stimulates Pancreatic Hypertmentioning

confidence: 86%

“…To determine changes in cell size we quantitated the density of nuclei stained with DAPI using Metamorph software as modified from a previous study (6). Four mice from each of the following conditions were analyzed for number of nuclei per unit area of mouse pancreas: wild-type and CCK receptor knockout mice on either normal diet or high-protein diet for 7 days.…”

Section: Methodsmentioning

confidence: 99%

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

Crozier

Sans

Wang

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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JA. CCK-independent mTORC1 activation during dietary proteininduced exocrine pancreas growth. Am J Physiol Gastrointest Liver Physiol 299: G1154 -G1163, 2010. First published August 26, 2010 doi:10.1152/ajpgi.00445.2009.-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.

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“…TORC1 was also shown to play a role in the hypertrophic response to feeding a high protein diet and this was independent of CCK (11). Conversely, pancreatic atrophy was seen in response to a loss of TORC1 signaling when mice were fed a protein free diet (9). These in vivo responses involve multiple hormones including CCK and insulin and nutrients acting directly, particularly amino acids.…”

Section: Mtor Signaling In Pancreatic Cellsmentioning

confidence: 99%

The mTOR Signaling Pathway and Regulation of Pancreatic Function

Williams¹

Pancreapedia: Exocrine Pancreas Knowledge Base

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Molecular Mechanisms of Pancreatic Dysfunction Induced by Protein Malnutrition

Cited by 30 publications

References 36 publications

Digestive Enzymatic Responses of Chickens Feed-restricted and Refed as Affected by Age

Digestive Enzymatic Responses of Chickens Feed-restricted and Refed as Affected by Age

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

The mTOR Signaling Pathway and Regulation of Pancreatic Function

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