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1. |
The Ileum and Carbohydrate‐Mediated Feedback Regulation of Postprandial Pancreaticobiliary Secretion in Normal Humans |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 495-505
Naresh Jain,
Michel Boivin,
Alan Zinsmeister,
Eugene DiMagno,
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摘要:
We investigated the effect of perfusing carbohydrate into the ileum on postprandial pancreaticobiliary secretion and the relationships among carbohydrate in the ileum, pancreaticobiliary secretion, and gastric emptying. Eighteen healthy volunteers were intubated with a multilumen oroileal tube. A metal labeled with111In-diethylenetriamine-pentaacetic acid (400 calories; 60% carbohydrate, 20% protein, 20% fat) was then infused into the stomach, and a carbohydrate solution (rice starch + glucose) was perfused into the terminal ileum at rates (mglmin) of 0 (saline; n = 6), 12.5 (n = 4), 25 (n = 4), 50 (n = 2), and 100 (n = 2). To prevent digestion of the carbohydrate in the ileum, an amylase inhibitor (3.3 mg/ml) was added to the perfusate used in half of the subjects. Postprandially, we measured outputs of amylase, trypsin, and bile acids in the duodenum, the amount of carbohydrate in the ileum, and gastric emptying. During the second postprandial hour the rate of gastric emptying was inversely related to the amount of carbohydrate in the ileum (p < 0.01) and was directly correlated with pancreaticobiliary secretion (p < 0.05). However, as the amount of unabsorbed carbohydrate in the ileum increased, the ratio of amylase to trypsin secretion increased (p < 0.005). Postprandially carbohydrate in the ileum induces changes of upper-gut function that should increase digestion and absorption of carbohydrate since gastric emptying (and delivery of carbohydrate to the duodenum) slows and pancreatic amylase secretion increases relative to trypsin secretion and gastric emptying.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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2. |
Growth and Differentiation of Pancreatic Acinar CellsIndependent Effects of Glucocorticoids on AR42J Cells |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 506-513
Janice Guthrie,
John Williams,
Craig Logsdon,
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摘要:
Dexamethasone (DEX) inhibits growth and induces differentiation in rat pancreatic acinar AR42J cells. We wished to determine whether growth and differentiation are mutually exclusive in AR42J cells and whether DEX effects on growth and differentiation are mutually dependent or independent. Inhibition of DNA synthesis, assessed by [3H]thymidine incorporation, was detectable after 6 h, half-maximal after 12 h, and complete after 18-h DEX treatment, at which time incorporation was reduced to 9.0% of control. The half-maximal effective dose for inhibition of DNA synthesis was 0.5 nM, and maximal inhibition was achieved with 10 nM DEX. This dose-response was similar to that previously reported for DEX-induced parameters of differentiation. The rank order of potency for inhibition of DNA synthesis by various steroid hormones was DEX > corticosterone > aldosterone > progesterone. Hydroxyurea or serum starvation inhibited growth to the same extent as DEX but did not induce differentiation. Moreover, hydroxyurea or serum starvation did not block the ability of DEX to induce differentiation. Addition of either EGF or insulin significantly reversed the growth inhibitory effects of submaximal (1 nM) DEX. In cultures released from growth inhibition, 1 nM DEX increased cellular amylase content 5.9- to 6.5-fold, similar to the amylase increase in growth-inhibited cultures. Therefore, growth inhibition and differentiation are independent delayed events regulated by DEX in AR42J cells.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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3. |
Rat Pancreatic Duct Epithelium Cultured on a Porous Support Coated with Extracellular Matrix |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 514-521
Thomas Heimann,
Sherwood Githens,
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摘要:
A method was developed for the isolation and culture of rat pancreatic duct epithelium of predominantly interlobular duct origin. Purified duct epithelial fragments were cultured on a porous support (HATF filters, Milli-pore) at 37°C in a 1:1 mixture of Dulbecco's Modified Eagle's and Ham's F-12 media supplemented with insulin, cholera toxin, epidermal growth factor, bovine pituitary extract (BPE), and Nu-Serum (Collaborative Research) in a humidified atmosphere of 95% air and 5% CO. The filters were coated with an extracellular matrix of either rat tail collagen or Matrigel (Collaborative Research), both of which significantly enhanced growth of the duct epithelium in comparison with untreated filters. The cells grew from the tissue fragments as epithelial islands, which merged to form a confluent sheet of epithelium covering at least 80% of the filter within 10 days in culture. The mitotic index of the spreading epithelium increased with time, reaching a maximum of 0.6% on days 3 and 5 and then declining. The epithelial monolayer consisted of tightly packed cells, with a few large cells and a few cells undergoing abnormal mitoses. Fibroblast contamination was negligible. The cells retained carbonic anhydrase activity, consistent with their pancreatic ductal origin and with the maintenance of differentiation in culture. The epithelium could be subcultured but with a low efficiency. A defined, serum-free medium was established with the addition of ethanolamine, bovine serum albumin, and transferrin and the deletion of serum and BPE. The epithelial cells grew nearly as well in this medium as in the serum-containing medium. This system may be of practical use as a method by which to define further the biochemical and physiological properties of pancreatic duct cells.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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4. |
Effect of L‐DOPA Administration on Islet Monoamine Oxidase Activity and Glucose‐Induced Insulin Release in the Mouse |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 522-527
Ingmar Lundquist,
Georgios Panagiotidis,
Anders Stenstrom,
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摘要:
Previous studies have shown that the amine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is rapidly converted to its corresponding amine, dopamine, in islet β-cells. In the present investigation, we studied the effect of acute L-DOPA administration on islet monoamine oxidase (MAO) activity and on glucose-induced insulin secretory response in mice. It was observed that at 2 min after intravenous L-DOPA administration, there was a marked increase (+ 35%) in islet MAO activity, with serotonin as substrate. At 7 min, MAO activity towards dopamine was enhanced by 32% and that towards serotonin and phenylethylamine (PEA) was decreased by 23 and 25%, respectively. The inhibitor of L-aromatic amino acid decarboxylase, benser-azide, abolished L-DOPA-induced changes of MAO activity, suggesting that the formed dopamine, and not L-DOPA itself, was responsible for the observed effects. At 60 min, no effect by L-DOPA administration on islet MAO activity was noticed. L-DOPA (125 or 250 pmol/kg), given together with glucose, induced a decrease in glucose-induced insulin response. L-DOPA (125 pmol/kg), given 7 min before glucose, totally suppressed glucose-induced insulin response. This inhibition was eliminated through pretreatment with benserazide. Enhancement of glucose-stimulated insulin response, after deposition of horseradish peroxidase (HRP) in p-cell vacuolar system, was suppressed by L-DOPA. We conclude that acute L-DOPA-induced dopamine accumulation in pancreatic islets is accompanied by rapid changes in MAO activity, concomitant with an inhibitory effect on glucose-stimulated insulin response. Increased hydrogen peroxide production, following increased MAO activity, may possibly augment the inhibitory effect of dopamine accumulation on insulin release.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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5. |
Selenium and Diabetes in the Tropics |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 528-533
S. Yadav,
J. Day,
V. Mohan,
C. Snehalatha,
J. Braganza,
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摘要:
We have examined the possibility that selenium deficiency may underlie one or more of the following peculiarities of chronic pancreatitis in tropical as compared to temperate zones: much higher prevalence, propensity for pancreatic calculi, and high frequency of diabetes. Selenium was measured by graphite furnace atomic absorption spectrometry in sera from 20 healthy volunteers, 36 patients with chronic pancreatitis (calcitic 35, diabetic 32), and 23 patients with primary forms of diabetes, from Madras, South India; results were compared with data from 41 controls and 37 patients with chronic pancreatitis (calcitic 13, diabetes 8) from Manchester, North West, England. We conclude that (a) bioavailability of selenium is equally high in each geographic area; (b) decrement in serum selenium (p < 0.001) is of a similar order in Manchester and Madras patients, which denies a connection with calculi formation or pancreatic exocrine failure (since the incidence of these two problems was substantially higher in the Madras series); and (c) selenium levels do not account for accelerated course to diabetes in tropical chronic pancreatitis.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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6. |
Effects of Feeding, Fasting, and Caerulein Treatment on Ornithine Decarboxylase in Rat Pancreas |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 534-541
Annik Langlois,
Jean Morisset,
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摘要:
Ornithine decarboxylase (ODC) is the rate-limiting enzyme in poly-amine biosynthesis. We examined circadian variations in pancreatic ODC activity and time-course effects of caerulein in fed and fasted rats. Significant circadian variations in amount of ODC activity were observed. The highest values were obtained during the dark period (1855 ± 406 pmoles CO2/h), and the lowest during the light period (359 ± 84 pmoles CO2/h). Caerulein treatment induced hypertrophy and hyperplasia of the pancreas in fed rats; increases in pancreatic ODC activity preceded the rise in protein and DNA contents (447 ± 44 pmoles CO2/h and 5573 ± 893 pmoles CO2/h, 6 and 12 h after the first injection of caerulein, respectively). In fasted rats, pancreatic ODC activity was very low (149 ± 37 pmoles CO2/h) and caerulein treatment induced a transient increase in this activity 12 h after the first injection; hypertrophy but not hyperplasia, of the pancreas was observed. In caerulein-treated fasted rats, refeeding during the night following a 48 h fasting period was not enough to increase either ODC activity or DNA content. These findings demonstrate that nutritional status is an important factor in the regulation of ODC activity and, thereby, in caerulein-induced pancreatic growth.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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7. |
Scanning Electron Microscopic Observations of Three‐Dimensional Structure of the Rat Pancreatic Duct |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 542-550
Nobuo Ashizawa,
Makoto Watanabe,
Shiro Fukumoto,
Yoshihiro Shimada,
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摘要:
To understand the fine, three-dimensional structure of the pancreatic duct, we made corrosion casts of rat pancreatic ducts and obtained biological specimens of rat pancreatic tissues for scanning electron microscopic observation. We observed the corrosion casts and the inner surfaces of the pancreatic duct specimens, using scanning electron microscopy. A comparative study between casts and specimens demonstrated the exactitude of our corrosion casts. These findings revealed the following facts: 1) The pancreatic ductal system had an almost tree-like shape, but parts of the intercalated ducts anastomosed with each other; 2) Intralobular ducts branched almost at a right angle from the interlobular ducts. Intercalated ducts, which branched off from the intralobular ducts, wound and forked into two branches, without any decrease in thickness. The intercellular secretory canaliculi extended from the central lumina, running straight through the center of the acini, close to the cell bases; 3) In pancreatic ducts, every lumen was covered with microvilli. The diameters of these microvilli were uniform (about 0.1 μm), but the heights were variable, even within a given pancreatic duct.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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8. |
Effects of Pancreastatin (24–49) on Growth of Normal Pancreas and Pancreatic Cancer |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 551-557
Jill Smith,
Scott Kramer,
Sagheed Bagheri,
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摘要:
In the present study, the effects of pancreastatin on growth are evaluated in two human pancreatic cancer cell lines, in vivo and in vitro, and on athymic nude mouse pancreas. SW-1990 and MIA PaCa-2 pancreatic cancer cell lines were grown in serum-supplemented and serum-free medium in the presence of pancreastatin (10−11-10−6M), or cholecystokinin (CCK) (10−11-10−8M) or combinations thereof. Growth was evaluated by [3H]thymidine incorporation and cell counts. Pancreastatin significantly inhibited DNA synthesis in both cell lines, and cell counts in SW-1990 on days 3 and 5 but not 7. CCK-stimulated cell growth was inhibited in both cell lines and mouse pancreas by pancreastatin. Pancreastatin had no effect in the presence of fetal bovine serum. In the in vivo experiments, pancreastatin (15 μg/kg) did not affect growth of SW-1990 xenografts to nude mice, but inhibited CCK-stimulated growth transiently. Pancreastatin (100 μg/kg) transiently decreased volumes of MIA PaCa-2 xenografts to nude mice and significantly decreased weight, protein, and DNA of mouse pancreas. Fasting glucose levels of mice treated with pancreastatin 100 pg/kg for 35 days were significantly lower than controls. Our results demonstrate that pancreastatin not only inhibits CCK-stimulated pancreatic growth but also has inhibitory effects by itself.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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9. |
Serum Immunoglobulin G Directed Against Porcine Trypsin in Pancreatic Insufficient Cystic Fibrosis Patients Receiving Pancreatic Enzyme Supplements |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 558-563
Richard Couper,
Steven Lichtman,
Geoffrey Cleghorn,
Virginia del Castillo,
Peter Durie,
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摘要:
Cystic fibrosis (CF) patients frequently malabsorb nutrients because of pancreatic failure. Standard therapy entails oral administration of porcine pancreatic enzymes, with meals. Porcine enzymes contain in excess of 25 potentially antigenic proteins. To evaluate antigenicity of one of these (porcine trypsin), we developed ELISA techniques capable of measuring total immunoglobulin G (IgG) and IgG directed against porcine trypsin in patient sera. Cross-sectional evaluation of sera from 12 controls and 41 CF patients showed that IgG directed against porcine trypsin was detectable in 12/17 CF patients receiving porcine enzymes (50.6 ± 56.0 ng/ml; range 0–154.0 ng/ml), while none was detected in controls or the 26 CF subjects not receiving enzymes. In the 17 CF patients receiving enzymes, porcine trypsin binding IgG contributed 0.85 ± 0.83% of the total IgG pool. Levels of porcine trypsin binding did not correlate with total IgG. Longitudinal evaluation was then performed in 26 CF patients, before and after commencement of enzyme therapy. Prior to commencing therapy, porcine trypsin binding IgG was undetectable in sera from 24/26 patients. Within 4.2 years of commencing therapy, 25/26 patients (96%) developed porcine trypsin binding IgG. Thus, serum IgG responses to porcine trypsin appear to be common in CF patients receiving porcine enzymes and contribute considerably to total IgG levels. Other individual enzymes in porcine extracts are likely to elicit similar antigenic response.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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10. |
Role of Cholecystokinin in Cholestyramine‐induced Changes of the Exocrine Pancreas |
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Pancreas,
Volume 6,
Issue 5,
1991,
Page 564-570
Irmtraut Koop,
Michele Lindenthal,
Michael Schade,
Michael Trautmann,
Guido Adler,
Rudolf Arnold,
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摘要:
This study was an investigation of the role of cholecystokinin (CCK) in the stimulatory action of cholestyramine on rat exocrine pancreas. Postprandial CCK release was significantly enhanced by acute administration of cholestyramine (12.7 ± 1.8 vs 3.7 ± 0.5 pmol/L in controls). Over four weeks, rats were fed either regular diet or diet containing 6% cholestyramine, and were treated with the specific CCK receptor antagonist L-364,718 (2 × 0.5 mgikg body weight/day s.c.) or DMSO (vehicle for the antagonist). Cholestyramine significantly increased pancreatic weight and trypsin and chymo-trypsin contents. L-364,718 abolished these effects. Concomitant administration of antagonist and cholestyramine elevated amylase content, compared to controls. CCK levels in fasted animals did not differ between the four groups. The effect of the same dose of L-364,718 on pancreatic enzyme depletion, induced by the protease inhibitor camostate, was studied in a control experiment. A single dose of camostate (200 mg/kg) caused a 4448% decrease in enzyme content. L-364,718 reversed this effect for all enzymes. We conclude that CCK is the mediator of cholestyramine-induced pancreatic hypertrophy and increase in content of proteases. After long-term administration, the CCK receptor antagonist, in combination with cholestyramine revealed an agonistic effect on individual, pancreatic enzyme content.
ISSN:0885-3177
出版商:OVID
年代:1991
数据来源: OVID
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