Role of cholecystokinin in induction and maintenance of dietary protein-stimulated pancreatic growth

Green, G. M.; Jurkowska, Grażyna; Bérubé, France-Line; Rivard, Nathalie; Guan, Difu; Morisset, Jean

doi:10.1152/ajpgi.1992.262.4.g740

Cited by 16 publications

(18 citation statements)

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“…It is believed that oral administration of protease inhibitor or dietary protein induces release of endogenous CCK, resulting in stimulation of pancreatic growth (17,18). To confirm the role of endogenous CCK in the pancreatic growth induced by camostat, we fed camostat to CCK-deficient mice for 10 days.…”

Section: Effect Of Camostat On Pancreatic Growth In Micementioning

confidence: 99%

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Calcineurin mediates pancreatic growth in protease inhibitor-treated mice

Tashiro¹,

Samuelson²,

Liddle³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Calcineurin mediates pancreatic growth in protease inhibitor-treated mice. Am J Physiol Gastrointest Liver Physiol 286: G784-G790, 2004. First published December 18, 2003 10.1152/ ajpgi.00446.2003.-CCK acts on pancreatic acinar cells to increase intracellular Ca 2ϩ leading to secretion of digestive enzymes and, in the long term, pancreatic growth. Calcineurin (CN) is a serine/ threonine-specific protein phosphatase activated by Ca 2ϩ and calmodulin that recently has been shown to participate in the growth regulation of cardiac and skeletal myocytes. We therefore tested the effect of two different CN inhibitors, cyclosporine A (CsA) and FK506, on mouse pancreatic growth induced by oral administration of the synthetic protease inhibitor camostat, a known stimulator of endogenous CCK release. Mice were fed a powdered diet with or without 0.1% camostat. Pancreatic wet weight, protein, and DNA were increased in response to camostat in a time-dependent manner over 10 days in ICR mice but not in CCK-deficient mice. Both CsA (15 mg/kg) and FK506 (3 mg/kg) given twice daily blocked the increase in pancreatic wet weight and protein and DNA content induced by camostat. The increase in plasma CCK induced by camostat was not blocked by CsA or FK506. Camostat feeding also increased the relative amount of CN protein, whereas levels of MAPKs, ERKs, and p38 were not altered. In summary, 1) CCK released by chronic camostat feeding induces pancreatic growth in mice; 2) this growth is blocked by treatment with both CsA and FK506, indicating a role for CN; 3) CCK stimulation also increases CN protein. In conclusion, activation and possibly upregulation of CN may participate in regulation of pancreatic growth by CCK in mice.cholecystokinin; camostat; FK506; cyclosporine A A VARIETY OF GASTROINTESTINAL peptides have been implicated in the regulation of proliferation and differentiation in the mature gastrointestinal tract and the pancreas (30,56). It is well known that feeding initiates pancreatic protein synthesis and secretion and that adaptation to a high-protein diet results in pancreatic growth (17, 18). More detailed studies have shown that among gastrointestinal peptides, CCK is released in response to dietary protein leading to pancreatic growth. Injection of CCK increases pancreatic wet weight and protein and DNA content in vivo over 4-10 days (8,37,40,43). Oral administration of soybean trypsin inhibitor (5, 44) or the synthetic protease inhibitor camostat (10,15,37,52,55), as well as pancreaticobiliary diversion (13, 39), increase the release of endogenous CCK into the blood and induce pancreatic growth. Moreover, CCK-A receptor antagonists that block the action of exogenous and endogenous CCK inhibit pancreatic growth (10, 13, 37, 39, 52). Therefore, most of the studies of pancreatic growth have been focused on CCK as a key regulator.In pancreatic acinar cells, the intracellular mechanisms of enzyme secretion have been well documented. CCK activates the release of intracellular Ca 2ϩ and the influx of Ca 2ϩ and generate...

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Section: Effect Of Camostat On Pancreatic Growth In Micementioning

confidence: 99%

“…It is well known that feeding initiates pancreatic protein synthesis and secretion and that adaptation to a high-protein diet results in pancreatic growth (17,18). More detailed studies have shown that among gastrointestinal peptides, CCK is released in response to dietary protein leading to pancreatic growth.…”

mentioning

confidence: 99%

Calcineurin mediates pancreatic growth in protease inhibitor-treated mice

Tashiro¹,

Samuelson²,

Liddle³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Although some experiments utilizing pharmacological CCK receptor antagonists in rats seemed to support this hypothesis (14,25), it has been demonstrated that rats fed high concentrations of amino acids, which unlike protein do not stimulate CCK secretion (21), have significant pancreatic hypertrophy (18). More definitively, Lacourse et al (20) generated a CCK-deficient mouse and demonstrated that pancreatic hypertrophy resulting from feeding a protein-enriched diet is similar in CCK-deficient mice and wild-type littermates.…”

mentioning

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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“…Switching from a 5-10% casein diet to one containing 70-75% casein caused an increase in pancreatic weight, protein and DNA content reaching a plateau in 7-14 days (40,41,91). This was accompanied by a transient increase in plasma CCK and the growth response could be partially blocked with a CCK antagonist (41,91).…”

Section: High Protein Dietmentioning

confidence: 97%

“…Until recently the most common technique was dissecting and weighing the pancreas. This yields values for young adults, usually males, fed a control diet, of 8-12 mg pancreatic weight/g body weight for mice (22,64,120,125,143), 22.5 mg PW/gBW for Syrian Hamster (124), 2.5-4 mg PW/g BW for rats (25,34,40,57,123,158), and 0.5-1.1 g PW/kg BW for adult humans (13,127). Note that the relative pancreas size gets smaller as the animal gets larger.…”

Section: Measurement Of Pancreatic Sizementioning

confidence: 99%

Regulation of Normal and Adaptive Pancreatic Growth

Williams¹

Pancreapedia: Exocrine Pancreas Knowledge Base

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Role of cholecystokinin in induction and maintenance of dietary protein-stimulated pancreatic growth

Cited by 16 publications

References 0 publications

Calcineurin mediates pancreatic growth in protease inhibitor-treated mice

Calcineurin mediates pancreatic growth in protease inhibitor-treated mice

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

Regulation of Normal and Adaptive Pancreatic Growth

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