cholecystokinin and Hyperplasia

Topics: Animals; Cholecystokinin; Gastrins; Gastrointestinal Hormones; Hyperplasia; Hypertrophy; Male; Pancreas; Pancreatic Juice; Rats; Rats, Inbred Strains

Since the subject of intestinal adaptation was last reviewed (16, 20, 97), there have been relatively few major advances but many useful minor additions and extensions which have helped to consolidate our knowledge of the field. The aim of this chapter is to summarise the results of a series of experiments which build up to our present state of knowledge. In doing so, the results of relatively old studies carried out some 15 years ago are briefly reviewed since they provide an essential background for, our current work. However, the article concentrates mainly on the new developments and in discussing these, areas of doubt and controversy are emphasised.

Topics: Adaptation, Physiological; Animals; Biliary Tract; Biological Transport, Active; Cholecystokinin; Dogs; Female; Hormones; Humans; Hyperplasia; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Lactation; Pancreas; Parenteral Nutrition, Total; Pregnancy; Rats; Secretin; Starvation

Cholecystokinin (CCK) stimulates secretion and evokes a hyperplastic response in the rat pancreas. The aims of this study were to measure the effect of chronic hyperCCKemia induced by pancreatico-biliary diversion (PBD) on pancreatic enzyme concentrations, on amylase secretion by dispersed acinar cells, and on the CCK-stimulated secretion of pancreatic juice in PBD-operated rats.. Forty-five Sprague-Dawley male rats had either PBD or sham operation 4 weeks before sacrifice or additional experiments. In the first study, 25 rats (13 PBD and 12 sham-operated rats) were either freely fed or fasted overnight before sacrifice. The pancreas was dissected out, weighed and analyzed. In the second study, the rats (6 PBD and 7 sham-operated rats) were fasted overnight before pancreatic acini were prepared. Secretion of amylase during stimulation of acini with CCK-8S and carbachol was measured. In the third study (5 sham-operated and 4 PBD rats), the rats were fasted overnight before basal and CCK-stimulated secretion was measured in vivo.. PBD-operated rats showed a threefold increase in pancreatic wet weight with increased contents of DNA, protein and water. The concentration of pancreatic amylase was 7-12% of that found in control animals. The concentrations of trypsin and lipase were also lowered. Stimulation of dispersed pancreatic acini with CCK-8S or carbachol resulted in secretion of amylase to a similar extent in PBD and sham-operated rats. There was no difference in the secretion of pancreatic juice in response to CCK, but although the output of amylase from PBD-operated rats increased with CCK, it remained at a low level throughout the study period.. PBD evoked hyperplastic changes in the rat pancreas and decreased the concentrations of amylase, trypsin and lipase. However, the capacity of acinar cells to secrete amylase remained intact. The stimulated pancreatic secretion was not changed in volume, but the output of amylase was low in PBD-operated rats. The findings are consistent with the idea that the enlargement of the pancreas following PBD does not improve the secretory capacity.

Topics: Amylases; Animals; Bile Ducts; Carbachol; Cholecystokinin; Hyperplasia; Male; Pancreas; Pancreatic Juice; Rats; Rats, Sprague-Dawley

Cholecystokinin (CCK) exerts trophic effects on the exocrine pancreas. Total parenteral nutrition (TPN) results in hypotrophy of the pancreas. The present study aimed to examine the effect of exogenous and endogenous CCK during TPN.. Seventy-two Sprague-Dawley rats were orally fed or given TPN after pancreaticobiliary diversion (PBD) and were infused with CCK-8S or the CCK-receptor antagonist devazepide for 7 days.. Infusion of CCK and PBD caused hyperCCKemia, whereas TPN did not influence the concentration of plasma CCK. The reduced pancreatic contents during TPN could be reversed by CCK but not by PBD. The hyperplastic response to CCK in orally fed rats was abolished during TPN. Devazepide did not influence the pancreatic variables in orally fed and TPN-treated rats.. TPN reduces the hyperplastic response of the exocrine pancreas to CCK, and CCK reverses the hypotrophy seen during TPN. The effects of CCK on the exocrine pancreas seems to need enteral nutrition for the full expression.

Topics: Animals; Benzodiazepinones; Biliopancreatic Diversion; Cholecystokinin; Devazepide; Hormone Antagonists; Hyperplasia; Male; Pancreas; Parenteral Nutrition, Total; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Sincalide

The present study was performed to examine the effect of ageing on pancreatic hyperplasia observed after proximal small bowel resection (PSBR). Young and old Wistar rats were randomly assigned to two groups, which underwent either an approximate 90% PSBR or a jejunal and ileal transection (TRC). One week after the operation, the pancreatic wet weight and the protein, DNA and RNA content of the pancreas were all significantly higher in young PSBR rats than in young TRC rats. However, no differences were seen in the old rat groups. Plasma enteroglucagon levels were elevated in both young and old PSBR rats, but the ratio of increase between the PSBR and TRC groups was significantly higher in young rats. Plasma cholecystokinin and gastrin levels did not increase after PSBR in either the young or old rats. These findings suggest that pancreatic hyperplasia observed after PSBR is attenuated by ageing, probably due to an insufficient increase in plasma enteroglucagon levels.

Topics: Aging; Amylases; Animals; Body Weight; Cholecystokinin; DNA; Eating; Gastrins; Glucagon-Like Peptides; Hyperplasia; Intestine, Small; Lipase; Male; Organ Size; Pancreas; Radioimmunoassay; Rats; Rats, Wistar; RNA; Trypsinogen

Cholecystokinin (CCK) reportedly induces both hyperplastic and hypertrophic changes in the pancreas. Blockade of the CCK receptor results in decreased pancreatic secretion and atrophy. The aim of this study was to evaluate the time-course of the effects of stimulation and inhibition of the CCK-A receptor in the rat exocrine pancreas. Male rats had infusion of sulfated CCK-8, the CCK-A receptor antagonist devazepide, or sodium chloride by osmotic minipumps. After 36 h, 3, 7, or 28 d the rats had ip injections of thymidine, and 1 h later they were sacrificed. The pancreas was excised, weighed, and its content of protein, DNA, water, and enzymes was analyzed. Histologic samples were prepared for autoradiography. Pancreatic weight, protein, and DNA were increased at 36 h after the start of CCK infusion and throughout the study period. CCK stimulation also increased the content of trypsin at days 3 and 28. The labeling index of pancreatic acinar cells was increased at 36 h. Blockade of endogenous CCK by the receptor antagonist devazepide led to decreased pancreatic weight from the third day of infusion, whereas the protein content was decreased from the seventh day. At day 28, the DNA content was decreased by devazepide. However, the labeling index of acinar cells decreased transiently already at 36 h. Neither CCK nor devazepide caused any changes of protein content:DNA content ratio during the study. Continuous infusion of CCK caused pancreatic hyperplasia already after 36 h. Stimulation up to 28 d did not cause any further effects. The adverse changes found after blockade of the CCK-A receptor showed much of the same time-course.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Devazepide; DNA; Hyperplasia; Male; Pancreas; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin

The present study evaluated pancreatotrophic factors after massive small bowel resection. Specifically, we examined the role of enteroglucagon in compensatory pancreatic hyperplasia after proximal small bowel resection (PSBR) by using rats fed a fiber-free elemental diet or an elemental diet containing pectin. PSBR increased the net pancreatic weight as well as the protein, DNA, RNA, and amylase contents, and elevated plasma enteroglucagon levels. Pectin addition to the diet provoked a further increase in these parameters and significant positive correlations were found between the plasma enteroglucagon levels and the protein, DNA, and RNA contents of the pancreas. Plasma gastrin and CCK levels were not affected by the small bowel resection. These results indicate that enteroglucagon may exert a potent trophic effect on the pancreas after PSBR.

Topics: Adaptation, Physiological; Amylases; Animals; Cholecystokinin; DNA; Gastrins; Glucagon-Like Peptides; Hyperplasia; Intestine, Small; Male; Organ Size; Pancreas; Proteins; Rats; Rats, Wistar; RNA

The effect of pancreaticobiliary diversion (PBD) on the colonic mucosa was studied in hamsters over 5, 10, and 24 days. Sham-operated animals served as controls. At all three time intervals, experimental animals had increased plasma cholecystokinin concentrations and decreased gastrin concentrations. Five days after PBD, there was an increase in scintigraphically measured [3H]thymidine incorporation into colonic tissue. Correspondingly, there was an increase in the [3H]thymidine DNA labeling index of goblet cells in the colonic mucosa. The total number of cells in the colonic crypt columns were significantly increased on days 5, 10 and 24. Whether this proliferative response in the colon is due to increased release of cholecystokinin, enteroglucagon, other aberrations of hormones or growth factors, or simply an increased bile load on the colonic mucosa remains to be clarified. Such further studies may reveal an alternative animal model for studies on risk factors in colonic carcinogenesis.

Topics: Animals; Autoradiography; Biliopancreatic Diversion; Cell Division; Cholecystokinin; Colon; Cricetinae; Gastrins; Hyperplasia; Intestinal Mucosa; Male; Mesocricetus; Organ Size; Thymidine; Time Factors; Tritium

Pancreatic trophism and pancreatic enzyme composition, and plasma levels of cholecystokinin, insulin, glucagon, and glucose in liver cirrhosis induced by chronic thioacetamide administration (0.02% in the drinking water for 12 mo) were studied in rats. Advanced liver cirrhosis was evident in all thioacetamide-treated rats. The weight of the pancreas and its contents of DNA, protein, trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor, and amylase were significantly increased as compared to the controls. The pancreatic secretory enzyme content changes showed a nonparallelism, characteristic of a cholecystokinin effect. Light and electron microscopy revealed a normal pancreatic architecture. Bioassayed plasma cholecystokinin levels in both fed and 24-h-fasted cirrhotic rats were significantly higher than in the corresponding controls. The plasma glucose, insulin, and glucagon levels demonstrated hypoglycemic tendencies with a glucagon predominance. These findings indicate that advanced liver cirrhosis in the rat is accompanied by pancreatic hypertrophy and hyperplasia, which might be attributed, at least in part, to elevated circulating cholecystokinin levels.

Topics: Animals; Blood Glucose; Cholecystokinin; DNA; Female; Hyperplasia; Liver; Liver Cirrhosis, Experimental; Pancreas; Proteins; Rats; Thioacetamide

The histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa are controlled by gastrin. An acute gastrin challenge induces release and accelerated resynthesis of ECL cell histamine. Long-term stimulation with gastrin causes ECL cell hyperplasia. We set out to study whether the ECL cells respond not only to gastrin but also to cholecystokinin (CCK). A wide dose range of gastrin-14 sulfated and -17 non-sulfated and CCK-8 sulfated (CCK-8s) and non-sulfated (CCK-8) was infused intravenously to rats for 3 h. The activity of the histamine-forming enzyme was measured at termination of infusion. Gastrins and CCK-8s were equally effective in activating the enzyme, whereas sulfated CCK-8 was notably less potent than the other three peptides. Clearly, the receptor responsible for activation of the ECL cells distinguishes poorly between gastrin-17 and CCK-8s, which is in line with the characteristics of the CCK-B receptor. Moreover, neither the response to gastrin-17 nor that to CCK-8s was affected by concomitant infusion of devazepide (200 micrograms/kg/h), a selective CCK-A-receptor antagonist. One group of rats received CCK-8s continuously via a minipump. Another group of rats was subjected to pancreaticobiliary diversion (PBD), which increases the plasma CCK concentration 10- to 20-fold. The rats were killed 7 or 10 weeks later, respectively, and the stomachs were analyzed with regard to mucosal growth and ECL cell hyperplasia. HyperCCKemic rats had increased pancreatic weights but showed no signs of growth stimulation in the stomach and no ECL cell hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Biliopancreatic Diversion; Cholecystokinin; Enterochromaffin Cells; Gastrins; Histidine Decarboxylase; Hyperplasia; Infusions, Intravenous; Male; Parietal Cells, Gastric; Rats; Rats, Sprague-Dawley; Stomach

This study was undertaken to clarify the role of endogenous cholecystokinin (CCK) in induction of pancreatic growth stimulated by a high protein diet. Rats with i.v. jugular cannulae in place and kept in Bollman cages were adapted to 5% casein diet for 9 days and switched to 70% casein for 2 days. MK-329, a CCK receptor antagonist, and SMS 201-995, a somatostatin agonist, were continuously infused at 0.5 mg/kg/h and 5 micrograms/kg/h, respectively, starting at the onset of feeding 70% casein. The 5 and 70% casein control groups were infused with saline. Feeding 70% casein significantly stimulated pancreatic hyperplasia and tissue hypertrophy. MK-329 and SMS 201-995 totally prevented 70% casein-induced increases in pancreatic weight and total RNA and DNA contents. The results indicate that endogenous CCK is the major factor responsible for pancreatic growth induced by a high protein diet.

Topics: Amylases; Animals; Benzodiazepinones; Body Weight; Caseins; Cholecystokinin; Chymotrypsinogen; Devazepide; Dietary Proteins; DNA; Hyperplasia; Octreotide; Organ Size; Pancreas; Proteins; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; RNA

The effect of unsulfated cholecystokinin on pancreatic growth was evaluated in two experimental models in vivo and in vitro. Mice were injected with sulfated cholecystokinin (CCKs) or unsulfated cholecystokinin (CCKu) (10 or 20 micrograms/kg) or vehicle twice daily for 15 days. Animals were then killed and pancreatic weights, protein, amylase, and DNA content were evaluated. In vitro, growth was evaluated by DNA synthesis and viable cell counts. MIA PaCa-2 and BxPC-3 human pancreatic cancer cells were treated with CCKs or CCKu (10(-12) to 10(-9) M) for 48 or 72 h in the presence of [3H]thymidine to evaluate DNA synthesis. Viable cell counts were performed on both cell lines grown in the presence or absence of unsulfated CCK (10(-12) to 10(-9) M) for 96 h. Pancreatic weight, protein, amylase, and DNA were significantly increased in animals treated with either CCKs or CCKu. However, pancreatic weight, protein, and amylase were significantly higher in mice treated with CCKs compared to CCKu (p less than 0.005). DNA content and index of hyperplasia were the same whether mice were treated with CCKs or CCKu. CCKu was as potent a stimulus for DNA synthesis as CCKs in MIA PaCa-2 and BxPC-3 cells. Finally, CCKu increased cell counts in both pancreatic cancer cell lines. These data suggest that the mechanisms responsible for CCK-induced growth of normal pancreas and pancreatic cancer may differ from those that regulate secretion.

Topics: Amylases; Animals; Cholecystokinin; DNA; Female; Humans; Hyperplasia; Mice; Mice, Inbred BALB C; Organ Size; Pancreas; Pancreatic Neoplasms; Proteins; Sulfates; Tumor Cells, Cultured

The effect of pancreaticobiliary diversion (PBD) with hypercholecystokininemia on the gastric fundic mucosa was studied in the Syrian golden hamster over 5 and 24 days. Sham-operated animals served as controls. Basal plasma gastrin concentrations were significantly decreased on days 5 and 24. Five days after PBD, there was a significant increase in the scintigraphically measured [3H]-thymidine incorporation into fundic tissue. Correspondingly, there was a significant increase in the number of cells with [3H]-thymidine-labeled DNA in the proliferative zone of the fundic mucosa. The total number of cells in the gastric pits, the number of cells in the proliferative zone and the proliferation index were also significantly increased 5 days after PBD. Although the mean values of all variables were higher after PBD than in the control group on day 24, these increases were not significant. It is concluded that PBD at least transiently stimulates gastric fundic epithelial proliferation in the hamster. Whether this is an effect of hypercholecystokininemia remains to be definitely proven in further studies.

Topics: Animals; Autoradiography; Biliopancreatic Diversion; Cell Division; Cholecystokinin; Cricetinae; Gastric Fundus; Gastric Mucosa; Gastrins; Hyperplasia; Male; Mesocricetus

The goal of the present studies was to identify and characterize the site of secretin action in the liver. Sections of normal and bile duct-ligated rat livers were used for in vitro 125I-secretin receptor autoradiography. Saturable binding was observed in both normal and bile duct-ligated livers but was much greater in the bile duct-ligated preparations. Binding was limited to biliary epithelium and the increased secretin binding observed in the ligated livers correlated with the increase in ductular tissue. Saturable binding was inhibited in a dose-dependent fashion by increasing concentrations of nonradioactive secretin. Analysis of saturation binding showed that 125I-secretin binding was best fit by a one-site receptor model with a Kd of 5.3 +/- 1.1 nmol/L. Glucagon, vasoactive intestinal polypeptide, gastric inhibitory polypeptide, growth hormone-releasing hormone, and cholecystokinin did not inhibit saturable 125I-secretin binding at concentrations of 1 pmol/L to 1 mumol/L. The authors conclude that high-affinity, specific secretin binding sites are present in rat intrahepatic biliary epithelium. When bile ducts are stimulated to proliferate by bile duct ligation, secretin binding is also increased.

Topics: Animals; Autoradiography; Bile Ducts; Binding Sites; Binding, Competitive; Cholecystokinin; Dose-Response Relationship, Drug; Epithelium; Gastric Inhibitory Polypeptide; Glucagon; Growth Hormone-Releasing Hormone; Hyperplasia; Liver; Male; Rats; Rats, Inbred Strains; Receptors, G-Protein-Coupled; Receptors, Gastrointestinal Hormone; Secretin; Vasoactive Intestinal Peptide

Using Syrian golden hamsters, we studied the effect of pancreaticobiliary diversion (PBD) on plasma cholecystokinin (CCK) and exocrine pancreatic tissue over 5, 10, and 24 days. As compared with sham-operated controls, PBD-operated animals had increased plasma CCK concentrations by 228, 318, and 207% at 5, 10, and 24 days, respectively. Correspondingly, pancreatic wet weight increased by 24, 61, and 87%; total pancreatic protein by 6, 57, and 73%; and total pancreatic DNA by 35, 52, and 98%, respectively. At 5 days, but not at 10 and 24 days, there was a significant increase in the pancreatic tissue DNA concentration (p less than 0.01) and [3]H-thymidine incorporation into DNA (p less than 0.02). Autoradiography showed increased [3]H-thymidine labeling index in acinar cells at 5 and 10 days after PBD (p less than 0.01 and p less than 0.005). Although not significant, ductal cell labeling index was also increased at 5 and 10 days. These findings provide evidence that, as in the rat, PBD in the hamster induces hypercholecystokininemia with ensuing pancreatic hyperplasia and hypertrophy. The hamster model may be useful for studies on the effect of endogenous CCK on pancreatic ductal cell carcinogenesis and diseases of the gallbladder, neither of which can be studied in the rat.

Topics: Animals; Cholecystokinin; Cricetinae; DNA; Hyperplasia; Male; Mesocricetus; Organ Size; Pancreas

1 Raw soya flour (RSF) in the diet induces pancreatic hypertrophy and hyperplasia in the rat, changes ascribed to production of a high circulating level of cholecystokinin (CCK) due to inhibition of trypsin in the duodenum. Prolonged ingestion results in pancreatic adenomas and carcinomas. 2 L-364, 718, a potent, highly specific CCK antagonist was used to investigate the short-term role of CCK. 3 In rats fed 50% RSF and L-364, 718 5 mg kg-1 p.o. twice daily for 4 d, there was inhibition of pancreatic hypertrophy and hyperplasia, which is further evidence that peripherally-acting CCK plays a major role in the generation of RSF-mediated changes in the pancreas.

Topics: Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Glycine max; Hyperplasia; Hypertrophy; Male; Mitosis; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin

Pancreaticobiliary diversion (PBD) caused a more than twofold increase in pancreatic weight after 10 days, with no further increase after 15 or 20 days or 7 weeks. Although the weight gain after PBD to a minor extent (10%) reflected increased water content, the main cause was hypertrophy and hyperplasia with increased pancreatic protein and DNA content. The cholecystokinin (CCK) concentrations in plasma were increased 10-fold from the 5th postoperative day. The trophic effects on the pancreas were completely abolished by the CCK antagonist L-364,718. Further, the antagonist caused a significant reduction in pancreatic weight, protein, and DNA in otherwise untreated controls. We conclude that PBD in rats induces trophic effects on the pancreas by increasing circulating CCK concentrations and that CCK is important for normal pancreatic growth.

Topics: Anastomosis, Surgical; Animals; Benzodiazepinones; Cholecystokinin; Devazepide; Hyperplasia; Hypertrophy; Ileum; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains

Bombesin has both direct and indirect effects [mediated through release of cholecystokinin (CCK)] on pancreatic secretion. Polyamine biosynthesis, essential for DNA synthesis, is increased in the pancreas after CCK stimulation. The purpose of this study was to examine the trophic effects of bombesin and to determine whether the mechanism of bombesin-induced pancreatic growth is mediated through synthesis of polyamines. The time course of bombesin-stimulated polyamine biosynthesis was defined. Rats were studied in groups of six and received intraperitoneal (i.p.) injections every 8 h of either saline, bombesin (10 micrograms/kg), CR1409 (2.5 mg/kg) (a CCK-receptor antagonist), or both to define the effects on pancreatic growth and polyamine biosynthesis. Rats were killed at 14 days and the pancreas was excised, weighed, and analyzed for protein, RNA, and DNA content. We found that bombesin produced significant pancreatic hyperplasia (increased pancreatic weight, protein, and DNA content) after 14 days. CR1409 inhibited only bombesin-stimulated DNA content. Bombesin stimulated polyamine biosynthesis as early as 2 h after administration of bombesin, but CR1409 had no effect. The trophic actions of bombesin are both direct and indirect (mediated through CCK), and the direct effects of bombesin are mediated by polyamine biosynthesis.

Topics: Animals; Bombesin; Cholecystokinin; DNA; Hyperplasia; Pancreas; Polyamines; Proglumide; Proteins; Putrescine; Rats; Receptors, Cholecystokinin; RNA; Spermidine; Spermine

Surgical diversion of bile and pancreatic secretions to the mid small bowel has been shown to provoke increased CCK plasma concentration and growth of the pancreas in rats. This study was undertaken to investigate the effects of chronic pancreaticobiliary diversion on pancreatic morphology as well as the circulating concentrations of pancreatic polypeptide, secretin, gastrin, and CCK. Fifteen month diversion provoked 73 and 86% increases in pancreatic weight and volume (p less than 0.001). Cholecystokinin blood concentration increased by 98%, from 20.9 +/- 5.7 pg/ml in controls to 41.3 +/- 5.4 after diversion (p less than 0.05), but pancreatic polypeptide, secretin, and gastrin levels were not affected. The volume of the exocrine pancreas doubled from 1104.6 +/- 78.2 mm3 in controls to 2201.2 +/- 229.2 (p less than 0.001), with a matching increase in interstitial tissue. On the contrary, the volume of the endocrine pancreas remained unchanged. Hyperplastic nodules developed in the exocrine pancreas, in 71% of diverted rats, but not in transected controls. We conclude from these observations that chronic diversion of bile and pancreatic juice stimulated pancreatic growth, most likely through a persistent rise of CCK plasma concentrations. Furthermore, this long lasting stimulation induced the development of exocrine pancreatic nodules.

Topics: Animals; Bile; Cholecystokinin; Hyperplasia; Male; Pancreas; Pancreatic Juice; Pancreatic Neoplasms; Rats; Rats, Inbred Strains; Time Factors

A diffuse peptide microcarcinoidosis was observed both in a 56-year-old man with chronic atrophic gastritis and in a 33-year-old female with chronic atrophic gastritis and pernicious anaemia. Besides hyperplasia of endocrine cells at the base of gastric fundus and corpus mucosa with infiltration of the mucosal muscular layer multiple macro- and micropolyp carcinoids were present. In both cases serotonin was demonstrated immunohistochemically in the intestinal metaplastic mucosal changes, in the microcarcinoidosis foci and in the carcinoids. However, no appropriate clinical symptomatology was observed. The diagnosis can already be made by biopsy which must be deep enough and include gastric mucosa containing the mucosal muscular layer. Should gastric carcinoid be established histologically the other macroscopically normal mucosa must also be biopsied for exclusion of diffuse microcarcinoidosis as intermediate form of a multiple carcinoid. In such a case treatment consists of total gastrectomy.

Topics: Adult; Anemia, Pernicious; Cholecystokinin; Female; Gastrectomy; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Humans; Hyperplasia; Male; Malignant Carcinoid Syndrome; Middle Aged; Serotonin; Somatostatin; Stomach Neoplasms

The evidence for and against an enteropancreatic trophic axis is reviewed. Luminal nutrition is essential for the maintenance of normal intestinal mucosal, and exocrine pancreatic, structure and function. Exclusion of luminal nutrition leads to mucosal hypoplasia and hypofunction with similar changes in the pancreas. The trophic effect of luminal nutrition may be mediated through the release of regulatory peptides with endocrine or paracrine effects. Enteroglucagon is the strongest candidate for the role of 'enterotrophin' while cholecystokinin (CCK) markedly influences pancreatic growth. Thus, CCK not only stimulates exocrine pancreatic secretion but makes acinar cells divide and the pancreas grow. The cellular mechanisms whereby trophic peptides influence normal and adaptive growth are also discussed with emphasis on polyamines (putrescine, spermidine and spermine) and the key enzymes controlling their synthesis (ornithine decarboxylase; ODC) and degradation (diamine oxidase; DAO). When polyamine synthesis is blocked with the ODC inhibitor, difluoromethyl ornithine (DFMO), the adaptive intestinal hyperplasia of pancreatico-biliary diversion is either inhibited or completely prevented. A proposed sequence of events might be as follows: luminal nutrients, particularly long-chain fats, reach the ileum and colon and stimulate increased enteroglucagon release. Enteroglucagon binds to cell receptors and triggers an intracellular cascade involving ODC and the polyamines, which, in turn, stimulate RNA polymerase, DNA, RNA and protein synthesis, cell division, and adaptive tissue growth.

Topics: Adaptation, Physiological; Amine Oxidase (Copper-Containing); Animals; Biliary Tract; Cholecystokinin; Eflornithine; Glucagon-Like Peptides; Hyperplasia; Intestinal Mucosa; Models, Biological; Ornithine; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Pancreas; Polyamines; Rats

Topics: Aging; Amylases; Animals; Body Weight; Cholecystokinin; Chymotrypsin; DNA; Hyperplasia; Hypertrophy; Lipase; Organ Size; Pancreas; Proteins; Rats; RNA; Stimulation, Chemical

Topics: Cholecystokinin; Diarrhea; Gastric Juice; Gastrins; Humans; Hyperplasia; Pancreatic Diseases; Peptides; Stomach