Relative Pancreatic Weight Research Articles

White Leghorn Chick의 초기 성장단계에서 소화기관의 발달, 소장의 소화 효소 및 간 조직의 항산화 방어작용

We aimed to investigate the age-dependent development of digestive organs, intestinal enzymes, and hepatic antioxidant defense system in White Leghorn chicks aged 0, 3, 7, 14, and 21 days. Body weight (BW) did not significantly change between days 0 and 7 but significantly increased (<i>P</i>&lt;0.05) after day 7. The relative liver weight (g/100 g of BW) was significantly lower at day 0 than at the other ages but markedly increased at days 3 and 7 (<i>P</i>&lt;0.05). The relative pancreatic weight changed similar to the change in liver weight, with the maximum development at 7 days (<i>P</i>&lt;0.05). The relative intestinal and mucosal tissue weights increased rapidly after hatching (<i>P</i>&lt;0.05), with the maximum growth at 7 days. Furthermore, maltase and sucrase activities were significantly higher at day 3 than at day 0 (<i>P</i>&lt;0.05). Leucine aminopeptidase activity was high at day 0 and remained constant as age increased. Superoxide dismutase and glutathione S-transferase activities in the liver were the lowest at day 0 but significantly increased after 7 days (<i>P</i>&lt;0.05). Glutathione peroxidase activity increased significantly after day 14 compared with that at days 0 and 7 (<i>P</i>&lt;0.05). Lipid peroxidation was not affected by age. In conclusion, the digestive organ weights and hydrolase activity of chicks increased rapidly during the first 3 or 7 days post-hatching. Hepatic antioxidant enzyme activity increased simultaneously with the increase in digestive organ weights, after 7 days.

Evaluation of protective effects of hydroalcoholic extract of Cassia fistula Linn. Pod on pancreas in streptozotocin-induced diabetic rats

Background: Diabetes mellitus (DM) is associated with oxidative stress. Medicinal plants and herbs are the rich sources of antioxidants which ameliorate oxidative stress-induced diabetic complications and could play an important role in the management of diabetes. Objective: The present study aimed to evaluate the protective effects of 70% ethanolic extract of Cassia fistula pod on pancreas in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Diabetes was induced in male Wistar rats by single intraperitoneal injection of STZ (60 mg/kg b.wt.). The diabetic rats were administered orally with C. fistula pod extract at three different doses (100, 250, and 500 mg/kg b.wt./day) for 60 days. The results were compared with standard drug glibenclamide (5 mg/kg b.wt./day) treated rats. Relative pancreatic weight and serum insulin level were determined. Histopathological changes and oxidative stress parameters, i.e., lipid peroxidation (thiobarbituric acid reactive substance [TBARS]) and antioxidative defense markers (superoxide dismutase, catalase, glutathione, and ascorbic acid), in the pancreas were investigated. Results: Oral administration of C. fistula pod extract (100, 250, and 500 mg/kg b.wt./day) or glibenclamide in diabetic rats significantly improved serum insulin level, total protein concentration, relative pancreatic weight, and mean diameter of islets of Langerhans as compared to diabetic control rats. Furthermore, treatment with extract also reduced TBARS levels and improved the levels of antioxidant markers in the pancreas. The histomorphological picture of the pancreas showed marked restoration of islets morphology. These results were comparable with glibenclamide. Conclusions: The results of the present study showed that C. fistula pod extract possesses significant antidiabetic activity though enhanced insulin secretion, improvement of antioxidative status of pancreas, and preservation of the integrity of pancreatic islets. Abbreviations used: b.wt.: Body weight; CAT: Catalase; DM: Diabetes mellitus; DNA: Deoxyribonucleic acid; GSH: Glutathione; ROS: Reactive oxygen species; SOD: Superoxide dismutase; STZ: Streptozotocin; TBARS: Thiobarbituric acid reactive substances.

Antioxidant, antihyperglycemic, and antidyslipidemic effects of Brazilian-native fruit extracts in an animal model of insulin resistance

ABSTRACTObjective: Insulin resistance (IR) plays an important role in the development of many diseases, such as diabetes mellitus. Therefore, the aim of the present study was to evaluate the effects of the extracts from fruits native to Brazil on metabolic parameters and hepatic oxidative markers in an animal model of insulin resistance induced by dexamethasone (DEX).Methods: Wistar rats received water or extracts of Eugenia uniflora or Psidium cattleianum, once a day for 21 days. For the last 5 days, the rats received an intraperitoneal injection of saline or DEX.Results: DEX caused a reduction in body weight gain and relative pancreatic weight, as well as glucose intolerance, and an increase in serum glucose and triacylglycerol levels. The extracts were found to prevent hyperglycemia and hypertriglyceridemia. DEX caused an increase in the levels of thiobarbituric acid-reactive substances and reactive oxygen species production in the liver of rats, and both extracts prevented these changes. In addition, hepatic glutathione peroxidase activity was reduced by DEX. However, total thiol content and activities of catalase, superoxide dismutase, and delta-aminolevulinate dehydratase were not altered in any of the tested groups.Conclusion: Fruit extracts of E. uniflora and P. cattleianum exhibited considerable antihyperglycemic, antidyslipidemic, and antioxidant effects, and may be useful in the therapeutic management of alterations due to IR.

Quercetin Curtails Obesity and Dyslipidemia, but Not Insulin Resistance in Long-Term Type 2 Diabetic Male Wistar Rats Fed the High-Fat, High-Sucrose Diet

It is unclear whether the persistence of Type 2 Diabetes (T2D)-associated insulin resistance in Wistar rats is entirely dependent on obesity and dyslipidemia or other factors are involved. We wanted to reveal whether alleviation of obesity and dyslipidemia by quercetin would sufficiently cure the insulin resistance in diabetic Wistar rats. For this purpose, ninety, male Wistar rats were randomized into three experimental groups (n=30): Normal Control (NC) fed chow diet, Diabetic Control (DC) fed High-Fat, High- Sucrose Diet (HFHSD) and diabetic, Quercetin-Treated (QT) fed the HFHSD and gavaged with quercetin at 50 mg.kg-1 bw.day-1. On Days 0, 60 and 120, Body Mass Index (BMI) and Abdominal Circumference:Thoracic Circumference (AC:TC) ratio were measured on ten rats from each group. Rats were then euthanized and fasting blood samples were withdrawn and used to quantify plasma glucose, Triacyclglycerols (TAG), LDL-cholesterol, total cholesterol, C-Reactive Protein (CRP) and insulin concentrations. Insulin resistance score, Relative Pancreatic Weight (RPW, %) and number of islet of Langerhans were also determined. We show that quercetin normalized BMI, AC:TC ratio, RPW (%) and dyslipidemia, and enhanced the islets number of Langerhans in the QT rats on Day 120 relative to the NC rats. In the diabetic DC rats, AC:TC ratio correlated positively with hyperglycemia and negatively with RPW (%). Quercetin lowered, but failed to normalize hyperinsulinemia, insulin resistance score, hyperglycemia and CRP in the QT rats relative to the NC rats suggesting that other factors are involved in the insulin resistance pathogenesis in T2D Wistar rats. Our data also suggest that AC:TC ratio is a predictor of the obesity-induced T2D in Wistar rats.

Use of unripe plantain (Musa paradisiaca) in the management of diabetes and hepatic dysfunction in streptozotocin induced diabetes in rats.

This study aims to investigate the effect of unripe plantain (Musa paradisiaca) on markers of hepatic dysfunction in streptozotocin induced diabetic rats. Blood glucose; relative liver weight (RLW); relative kidney weight (RKW); relative heart weight (RHW); relative pancreatic weight (RPW); serum and hepatic serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP); serum amylase, lipase, total, and conjugated bilirubin; and chemical analysis of the test feed were determined using standard techniques. The diabetic rats had significant alteration (P < 0.05) of blood glucose; RLW; RKW; RPW; serum and hepatic AST, ALT, and ALP; serum total and conjugated bilirubin; and serum lipase activities compared with nondiabetic while these parameters were significantly improved (P < 0.05) in the rats fed unripe plantain. There were no significant differences (P > 0.05) in the RHW of the rats in the three groups, as well as significant decreases (P < 0.05) in the amylase levels of the diabetic rats compared with the nondiabetic, but there was nonsignificant increase (P > 0.05) in the amylase levels of the rats fed unripe plantain compared with the nondiabetic rats. The test and standard rat feeds contained considerable amount of proteins, carbohydrates, fats, phenols, and crude fiber. Amelioration of acute pancreatitis by unripe plantain could play a key role in its management of diabetes and related complications.

Biochemical basis of the use of cocoyam (Colocassia esculenta L.) in the dietary management of diabetes and its complications in streptozotocin induced diabetes in rats

ObjectiveTo investigate the biochemical basis of the anti-diabetic action of cocoyam [Colocassia esculenta (C. esculenta)] in streptozotocin diabetic rats. MethodsBlood glucose of the rats was measured with a glucometer. The relative heart weight, relative pancreatic weight, serum proteins, urea, creatinine, albumin, amylase, lipase, serum and hepatic aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and chemical analysis of the test feed were determined using standard techniques. ResultsThe diabetic rats fed with cocoyam had significant elevation (P<0.05) of relative pancreatic weight, hepatic AST, ALT, ALP and serum proteins and albumin, but had significant reduction (P<0.05) of blood glucose, serum urea, creatinine, amylase, lipase, AST, ALT and ALP compared with the diabetic control rats while these parameters were significantly altered (P<0.05) in the diabetic control rats compared with the non-diabetic rats. There were no significant differences (P>0.05) in the relative heart weights of all the rats in the three groups. The test feed contained considerable amounts of phenolics, crude fiber, Ca, Fe, K, Na but low amounts of oxalate and phytate. ConclusionsC. esculenta may exert its anti-diabetic action by delaying/regulating the rate at which dietary starch is hydrolyzed to glucose or possibly through inhibition of acute pancreatitis. Finally, the study also shows the potentials of C. esculenta in the dietary management of obesity.

Ameliorative Potentials of Cocoyam (Colocasia Esculenta L.) and Unripe Plantain (Musa Paradisiacal L.) in Renal and Liver Growth in Streptozotocin Induced Diabetic Rats

The ameliorating potentials of cocoyam (Colocasia esculenta L.), ginger (Z.officinale Roscoe) and unripe plantain (Musa paradisiacae L.) incorporated feeds on the relative pancreatic weights of streptozotocin induced diabetic rats was investigated. The blood glucose level of all the rats was measured with a glucometer, the assay of the phytochemical and crude fibre compositions of the test feeds were carried out using standard techniques. The administration of the test feeds for 21 days to the diabetic rats of groups 5 to 7, resulted in 58.75%, 29.81% and 38.13% decreases in their hyperglycemia. Administration of the cocoyam incorporated feeds to the diabetic rats of group 5, resulted in 2.71% and 19.52% increases in their body weights and growth rates respectively, administration of the ginger incorporated feeds to the diabetic rats of group 6, resulted in 9.88% and 60.24% increases in their body weights and growth rates, unlike the diabetic rats of group 7, administered unripe plantain feed that had 5.12% decrease in weight with a corresponding 29.52% decrease in growth rate but higher than the diabetic control rats that recorded 28.69, 28.62% and 29.46% decreases in body weights with corresponding 248.9%, 239.9% and 250.14% decreases in growth rates. Chemical analysis of the test feeds indicate that they contained considerable amounts of phytochemicals and crude fibre. Results indicate the ability of cocoyam, ginger and unripe plantain to ameliorate the relative pancreatic weight of diabetics.

α-Tocopherol Treatment Ameliorates Chronic Pancreatitis in an Experimental Rat Model Induced by Trinitrobenzene Sulfonic Acid

Objective:To investigate the effects of α-tocopherol on pancreatic fibrosis and survival in rats with experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid (TNBS). Methods: Chronic pancreatitis was induced in male Sprague-Dawley rats by infusion of TNBS into the pancreatic duct. α-Tocopherol (300, 600 or 900 mg/kg) was orally administered to rats with experimental pancreatitis (treatment group) daily for 4 weeks. The relative pancreatic weight, pancreatic pseudocyst and death rate were observed. Paraffinembedded tissue samples were sliced, stained by hematoxylin-eosin and histopathologically examined. Results: α-Tocopherol administration significantly ameliorated the pancreatic weight loss induced by TNBS in chronic pancreatitis rats compared to the control group. There were pancreatic pseudocysts in 69% of the α-tocopherol group, and in 100% of the control group. α-Tocopherol administration led to a significant increase of the survival rate. The histopathologic scores were higher in the control group than in the α-tocopherol group. Subgroup analysis of histopathologic scores revealed that a high dose of α-tocopherol results in less pancreatic injuries. Conclusion: α-Tocopherol treatment elevates survival rate, extenuates fibrosis and increases relative pancreatic weight in the chronic pancreatitis model. α-Tocopherol therapy in chronic pancreatitis is now required to confirm these findings and establish the role of this treatment in the management of this disabling condition.

Nutritional and Biochemical Assessment of Field Peas (Pisum sativum L.) as a Protein Source in Poultry Diets

The effects of cultivar on the nutrient profile and protein quality of field pea (Pisum sativum) was investigated. A total of 19 samples representing five cultivars of field pea (Santana, Miami, Rex, Crusader and Courier) were analysed for proximate, fibre and carbohydrate components, minerals and amino acids. Starch was the major carbohydrate component in field pea, but it also contained significant quantities of non-starch polysaccharides. The pea protein was deficient in lysine, methionine, cystine and threonine. The results from the protein quality assay showed that there were no differences (P>0.05) in protein quality between pea cultivars. Compared to raw field pea, raw soybeans had a lower (P<0.05) protein efficiency ratio, and had higher (P<0.05) relative pancreatic weights and mortality rate, suggesting that raw soybeans contained high concentrations of anti-nutritional factors, especially protease inhibitors. Mortality of birds fed raw forms of field pea was low, suggesting that field pea do not have significant levels of any anti-nutrients. The relative pancreatic weights of birds fed pea diets also indicate that the level of protease inhibitors in pea cultivars tested were probably low. Overall, the present results demonstrate the nutritional potential of field pea as a protein source in poultry diets.

Acetyl-l-Carnitine Ameliorates Caerulein-induced Acute Pancreatitis in Rats

In the present study, we have addressed the possible protective role of acetyl-L-carnitine in caerulein-induced acute pancreatitis in male Swiss albino rats. Acute pancreatitis paradigm was developed by challenging animals with a supramaximal dose of caerulein (20 microg/kg, SC) four times at hourly intervals. Caerulein induced acute pancreatitis that was well-characterized morphologically and biochemically. Severe oedema with marked increased relative pancreatic weight, marked atrophy of acini with increased interacinar spaces, vacuolization, and extensive leucocytic infiltration were diagnostic fingerprints of the pancreatitis phenotype. A biochemical test battery that confirmed the model comprised increased plasma amylase and lipase activities, calcium levels as well as increased pancreatic enzymatic myeloperoxidase and glutathione-S-transferase activities, beside increased pancreatic contents of nitric oxide and malondialdehyde and reduced pancreatic glutathione level. Prior administration of acetyl-L-carnitine (200 mg/kg, IP) for seven consecutive days ahead of caerulein challenge alleviated all the histological and biochemical manifestations of acute pancreatitis. These results suggest a possible protective role of the carnitine ester in such a murine acute pancreatitis model probably via regulation of the oxidant/antioxidant balance, beside modulation of the myeloperoxidase and nitric oxide systems, which are involved in the inflammatory cascade that most often associate the disease.

Establishment of Animal Models for Three Types of Pancreatitis and Analyses of Regeneration Mechanisms

To investigate the mechanisms underlying the onset and progress of pancreatitis, 3 animal models (chronic, acute, and severe pancreatitis) were established by double ligature of the pancreatic duct, injection with cerulein, or injection with cerulein + double ligature of the pancreatic duct. We prepared a control and 3 experimental groups: group 1 (untreated control), group 2 (a chronic pancreatitis model; the pancreatic tail was exposed through a midline incision, and the pancreatic duct from this part was double-ligated), group 3 (an acute pancreatitis model; cerulein was intraperitoneally injected 7 times on day 0), and group 4 (a severe pancreatitis model; the double ligature of the pancreatic duct plus injection of cerulein). Kinetic observations of survival rate, relative pancreatic weight, and the macroscopical and microscopical diagnoses and observations of the changes in endocrine function clearly show that these 3 murine models of pancreatitis can serve as human models for chronic, acute, and severe pancreatitis. Furthermore, pancreas duodenum homeobox 1, cytokeratin 19, and Ki67 are expressed at the site of injury in the pancreas, resulting from the injection with cerulein and/or double ligature of the pancreatic ducts and indicating that there remains a tissue-regenerative capacity. These 3 mouse models could serve as human models for chronic, acute, and severe pancreatitis. Furthermore, cells of the epithelial lineage might participate in tissue regeneration in chronic, acute, and severe pancreatitis.

Soya-bean agglutinin induced both direct and cholecystokinin-mediated pancreatic enzyme synthesis in rats

AbstractThis study was conducted to examine the relationship between soya-bean agglutinin and cholecystokinin in stimulating pancreatic enzyme synthesis in rats. In experiment 1, 30 rats were given daily gastric infusions of 0, 3·5, 7·0, 10·5, or 14·0 mg of soya-bean agglutinin (no.=6) for 14 days. Compared with the control group, soya-bean agglutinin reduced weight gains, enhanced absolute and relative dry pancreatic weights, elevated serum cholecystokinin levels, and stimulated cholecystokinin mRNA expression in the intestine (P&lt;0·001). Pancreatic nucleic acid composition and the pancreatic activities of the enzymes amylase, trypsin and chymotrypsin all increased in response to increasing levels of soya-bean agglutinin (P&lt;0·001). In experiment 2, duodenal cells obtained from two rats were incubated at 37°C with either saline, 100 μg/ml soya-bean agglutinin, or a mixture of 100 μg/ml soya-bean agglutinin and 10 mmol/m of the L-type, calcium channel antagonist verapamil. Soya-bean agglutinin stimulated cholecystokinin mRNA expression and cholecystokinin release from small intestinal mucosal cells, and the effect was attenuated by verapamil. In experiment 3, pancreatic acinar cells, obtained from three rats, were incubated at 37 °C with either saline, or cholecystokinin (100 fmol/ml) and soya-bean agglutinin (1000 fmol/ml), either alone or in combination. Amylase, trypsin, and chymotrypsin activities from both culture media and acini cells were stimulated by both the soya-bean agglutinin and the cholecystokinin treatments. Enzyme activities, when the two factors were incubated in combination, were intermediate to those obtained when the factors were incubated alone. This suggesting that soya-bean agglutinin may depress the action of cholecystokinin on pancreatic enzymatic activities. In summary, soya-bean agglutinin appears to stimulate pancreatic enzyme synthesis both directly and also through a cholecystokinin-mediated pathway.

Duodenogastric reflux enhances growth and carcinogenesis in the rat pancreas.

Surgery for peptic ulcer disease may increase the risk of pancreatic cancer. The effect of duodenogastric reflux on pancreatic carcinogenesis was tested, and changes in the circulating levels of cholecystokinin (CCK) and gastrin were measured. Male Wistar rats (n = 40) weighing 250-300 g were randomized to undergo gastrotomy (control) or split gastrojejunostomy (to produce complete duodenogastric reflux) and then to receive azaserine (30 mg/kg/week intraperitoneally) or saline injections for 3 weeks. At 6 months, blood CCK was assayed and the pancreas was excised for quantitative estimation of atypical acinar cell foci (AACF), the precursor lesions of carcinoma. Rats that had undergone split gastrojejunostomy weighed 15-19 per cent less than controls (P < 0.05), but their relative pancreatic weight (mg pancreas per 100 g body-weight) was 52-60 per cent greater (P < 0.001). Acidophilic AACF occurred only in azaserine-treated rats with duodenogastric reflux. Although plasma CCK concentrations were unchanged, split gastrojejunostomy increased basal and postprandial gastrin levels by 98-175 per cent (P < 0.05). Duodenogastric reflux produces sustained hypergastrinaemia and promotes experimental pancreatic carcinogenesis.

Effect of dietary protein level, amino acid balance and feeding level on growth, gastrointestinal tract, and mucosal structure of the small intestine in broiler chickens

In a factorial experiment, two series of feeds containing excess dietary protein, differing in amino acid balance (i.e. balanced (BPS) and unbalanced (UPS) amino acid mixture), and with a range of protein contents (400, 300 and 200 g CP·kg -1 ) at the same energy content of 13 MJ AME·kg -1 were offered at two levels of feeding (ad libitum or 0.75 of ad libitum intake) to 4320 broiler chickens between 10 and 24 days of age. Growth rate was significantly lowered by feed restriction. There was also a significant (P < 0.001) effect of dietary protein on the combined weight of the proventriculus and gizzard but only for the birds on the restricted feeding regime. Relative pancreatic weight in- creased (P < 0.001) with an increase in dietary protein level for the birds fed restricted amounts of BPS. The crypt depth of chicks on the ad libitum feeding regime was higher (P < 0.01) for the chicks on the BPS than for those on the UPS diet. The protein content of the jejunal mucosa was higher (P < 0.001) for birds fed ad libitum on the UPS diet than on the BPS diet. Daily feed allocation had a significant (P < 0.01) effect on jejunal protein content in birds that received the BPS diet, this being reduced in birds on restricted feeding. Maltase (P < 0.001) and sucrase (P < 0.01) activities were sig- nificantly reduced in chicks offered ad libitum access to the UPS diet. At high dietary CP, the specific activity of alkaline phosphatase was lower (P < 0.001) in chicks on the UPS diet than in those fed the BPS diet.

Consumption of diets containing raw soya beans (Glycine max), kidney beans (Phaseolus vulgaris), cowpeas (Vigna unguiculata) or lupin seeds (Lupinus angustifolius) by rats for up to 700 days: effect on body composition and organ weights

Feeding trials have been done with rats to assess the effects of long-term (700 d) consumption of diets based on raw cowpeas (Vigna unguiculata; moderate Bowman-Birk inhibitor content, low lectin content), lupin seeds (Lupinus angustifolius; low lectin and protease inhibitor content) or soya beans (Glycine max; high Kunitz inhibitor content, moderate Bowman-Birk inhibitor content, moderate lectin content) or diets containing low levels of raw kidney bean (Phaseolus vulgaris; high lectin content, low Bowman-Birk inhibitor content) on body weight and composition and organ weights. All the legume-based diets reduced feed conversion efficiency and growth rates during the initial 250 d. However, after 250 d the weight gains by rats given legume-based diets were similar to those of controls given the same daily feed intake. Long-term consumption of diets containing low levels of kidney bean significantly altered body composition of rats. The levels of lipid in the body were significantly reduced. As a result, carcasses of these rats contained a higher proportion of muscle/protein than did controls. Small-intestine relative weight was increased by short- and long-term consumption of the kidney-bean-based diet. However, the increase in relative pancreatic weight observed at 30 d did not persist long term. None of the other legume-based diets caused any significant changes in body composition. However, long-term exposure to a soya-bean- or cowpea-based diet induced an extensive increase in the relative and absolute weights of the pancreas and caused an increase in the incidence of macroscopic pancreatic nodules and possibly pancreatic neoplasia. Long-term consumption of the cowpea-, kidney-bean-, lupin-seed- or soya-bean-based diets by rats resulted in a significant increase in the relative weight of the caecum and colon.

Inhibitory effect of a cholecystokinin antagonist on pancreatic carcinogenesis after pancreatobiliary diversion

The role of cholecystokinin (CCK) has been explored in pancreatic carcinogenesis following pancreatobiliary diversion (PBD), using the specific CCK receptor antagonist CR-1409. Male Wistar rats (n = 80) weighing 70-100 g were given weekly i.p. injections of azaserine (30 mg kg-1 week-1) for 3 consecutive weeks. One week later animals were randomised to receive either PBD or sham PBD and thereafter to receive s.c. injections of either saline or CR-1409 (10 mg kg-1 day-1, 5 days a week). Six months after operation surviving rats were killed as follows: sham + saline 20, PBD + saline 19, sham + CR-1409 14, PBD + CR-1409 11. Cardiac blood was taken for CCK assay and the pancreas was excised for wet weight measurement and quantitative estimation of atypical acinar cell foci (AACF), the precursor of carcinoma. PBD reduced median body weight (3-20% less than shams) but trebled the absolute and relative pancreatic weights (P < 0.001). CR-1409 blunted this adaptive response to PBD, reducing absolute pancreatic weight by 35% (P < 0.005). PBD quadrupled circulating CCK concentrations, regardless of the antagonist treatment. Acidophilic AACF occurred only in rats with PBD. CR-1409 markedly reduced the number of observed acidophilic AACF by 90% (P < 0.001) and the number of foci per pancreas by 93% (P < 0.001). Moreover, CR-1409 reduced the mean focal diameter of each lesion by 18% (P < 0.005), the mean focal volume by 58% (P < 0.05) and the percentage of pancreas occupied by acidophilic foci by 95% (P < 0.001). PBD enhances pancreatic carcinogenesis by causing hypercholecystokininaemia, and CR-1409 largely inhibits this enhancement.

Does vagotomy affect the growth of the pancreas in the rat?

Vagotomy has been claimed to have a growth-promoting effect on the pancreas in the rat. The present study failed to show differences in total or relative pancreatic weight and DNA content between vagally intact and vagally denervated rats, whether normoCCKemic or hyperCCKemic after pancreaticobiliary diversion during 2-8 weeks. Contrary to the claims made in several recent reports, vagotomy does not seem to influence the growth of the rat pancreas.

Effects of castration, alone and in combination with aminoglutethimide, on growth of (pre)neoplastic lesions in exocrine pancreas of rats and hamsters

We studied the effects of hormonal manipulation by orchiectomy, alone or in combination with the aromatase inhibitor aminoglutethimide (AGT), and by luteinizing hormone-releasing hormone agonist (LH-RH-A) (goserelin) treatment on the development of early putative (pre)neoplastic lesions induced in the pancreas of rats and hamsters by azaserine and N-nitrosobis(2-oxopropyl)amine respectively. Treatment of the animals started 1 week after the last injection with carcinogen and continued for 4 months. Orchiectomy caused a significant inhibition of growth of acidophilic atypical acinar cell nodules in the rat model, whereas surgical castration did not show an effect in the hamster model. In rats, but not in hamsters, orchiectomy resulted in a significant decrease in body weight and in absolute, but not relative pancreatic weight. Treatment of the animals with AGT or goserelin did not cause a significant effect on the development of either putative preneoplastic acinar lesions in rat pancreas or early ductular lesions in hamster pancreas. Hamsters showed clearly higher plasma epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) concentrations than rats, while plasma testosterone levels were significantly lower. Plasma EGF and IGF-1 levels decreased with increasing age in both control and treatment groups. Compared to controls there were no clear unequivocal effects of treatment on EGF, IGF-1 and gastrin levels. Plasma testosterone levels decreased by orchiectomy and LH-RH-A treatment. In rats hormone-induced effects on food intake and altered nutritional status might be important with respect to the development of carcinogen-induced preneoplastic pancreatic lesions.

Pancreatobiliary diversion enhances experimental pancreatic carcinogenesis

Since compensatory hyperplasia promotes experimental carcinogenesis in the gut, we tested the ability of two surgical models of pancreatic growth to promote pancreatic carcinogenesis. Male Wistar rats (n = 60) weighing 250-300 g underwent pancreatobiliary diversion (PBD), 90% small bowel resection (PSBR) or triple transection and reanastomosis of the small intestine (controls). Postoperatively, each group received azaserine (20 mg kg-1 wk-1 i.p.) for 6 weeks. Surviving rats were killed at 6 months, pancreatic wet weight was measured and histological sections were examined for atypical acinar cell foci (AACF), the putative precursor of carcinoma. Median relative pancreatic weight (mg pancreas/g body weight) was 2.20 for controls (n = 18), 4.08 for PSBR (n = 11) (P less than 0.001) and 6.86 for PBD (n = 16) (P less than 0.001). PSBR did not affect the development of acidophilic AACF, but PBD produced an enormous increase in their number per cm3 (median 96 vs. 0; P less than 0.001) and a 7-fold increase in their volume (P less than 0.001). Both operations cause pancreatic growth, but only PBD promotes carcinogenesis, possibly because of its unique hormonal effect.

Enzyme-specific activities and mineral concentrations of the exocrine pancreas from female SHR/N-corpulent (cp) rats.

A new rodent model, SHR/N-cp, for study of non-insulin-dependent diabetes mellitus (NIDDM) has recently been developed. The present study reports exocrine pancreatic enzyme activities and mineral concentrations in female corpulent (cp/cp) and lean (+/?) rats fed a diet containing carbohydrate as cooked corn starch or sucrose for 7 months to determine the potential of the model for studies of diet and pancreatic function in NIDDM. Although corpulent female rats weighed 2.5 times more than their lean littermates, they consumed less calories when expressed per 100 g body weight than lean rats. Corpulent rats had a significantly smaller relative pancreatic weight than lean rats (p less than 0.0001), but had greater total pancreatic DNA content and concentration (p less than 0.003) and higher pancreatic amylase (p less than 0.0001), lipase (p less than 0.0011), and chymotrypsinogen (p less than 0.0208) specific activities. Corpulent rats had a significantly lower pancreatic copper concentration than their lean littermates (p less than 0.0193). Corpulent rats consuming starch had a higher pancreatic iron concentration than all other experimental groups (p less than 0.05). The corpulent female rats were only mildly diabetic based upon serum and urine indices. The data suggest that the female SHR/N-corpulent rat may be a useful model for studying exocrine pancreatic function of mild cases of non-insulin-dependent diabetes.