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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kinetics of insulin secretion in response to glucose were studied in the in vitro perfused rat pancreas before and after removal of islet cell tumors induced by streptozotocin and nicotinamide. In addition, insulin secretion before and after tumor removal was compared with that from normal pancreata before and after sham operations, respectively. Thus, the two pancreas preparations were subjected to repeated perfusions with glucose. Perfusion of pancreata containing tumors with 8.4 mM glucose resulted in biphasic release in a pattern similar to that of normal pancreas. However, both basal and stimulated insulin secretion of tumor-bearing pancreata were greater than either those of pancreata from which tumors had been excluded by ligature or those of normal pancreata before sham operation. A second increase in the concentration of glucose from 2.8 to 8.4 mM also produced a biphasic release of insulin from extratumoral pancreata as well as from sham-operated normal pancreata. However, the insulin secretory response to glucose of extratumoral pancreatic tissue was less than that of control pancreatic tissue. Our findings indicate that pancreatic islet cell tumors induced by streptozotocin and nicotinamide respond to glucose with typical biphasic insulin release. Thus, chemically induced rat insulinomata may provide a readily available and valuable model of insulin-secreting tissue, analogous to normal islets. Furthermore, our study suggests that the B cell function of pancreata containing tumors is inhibited by the preexisting tumor-induced hyperinsulinism or by its metabolic consequences.
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PMID:Insulin release from the isolated perfused rat pancreas containing insulinomata induced by streptozotocin and nicotinamide: effects of glucose and responses to tumor removal. 626 93

This paper describes an inhibitory effect of propranolol on insulin secretion in rats with pancreatic islet cell tumors which have been induced by streptozotocin (65 mg/kg body weight) and nicotinamide (500 mg/kg). Following glucose ingestion (3 g/kg), propranolol (4 mg/kg) was injected into the tumor-bearing rats. Plasma insulin decreased paradoxically despite an increase in blood glucoses. In contrast, propranolol did not suppress insulin secretion in normal rats. The drug was found to have no effect on glucagon secretion in either experimental or control animals during glucose load. This may suggest that the experimentally induced insulinoma in hypersensitive to propranolol for inhibiting insulin secretion.
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PMID:Effect of propranolol on glucose-induced insulin response in rats with insulinomas. 626 20

The effect of syngeneic transplantation of islet tumors induced by streptozotocin-nicotinamide treatment into Fisher inbred diabetic rats was studied. Transplantation of 10 mg of tumor tissue under the kidney capsule of severely diabetic animals resulted in complete amelioration in 9 of 14 animals. Partial improvement was noted in three animals, whereas only one animal showed no change in diabetic condition within 4 months. Improvement in diabetes was accompanied by gain in body weight, decrease in blood sugar level and urinary glucose excretion, and normalization of glucose tolerance. After removal of the kidney containing the tumor grafts, the animals reverted to a severe diabetic condition, suggesting that the tumor graft supplied the insulin needs of the diabetic animals. The graft tissue exhibited in vitro insulin synthesis and secretion in response to 16.7 mM glucose.
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PMID:Reversal of diabetes by the isotransplantation of nicotinamide-streptozotocin-induced islet adenoma in rats. 627 54

Blood samples from closely monitored patients at the Veterans Administration Hospital in Houston, Texas, were collected, coded, and sent to Microbiological Associates over an 8-month period. Lymphocytes were isolated and cryopreserved at -190 degrees. Lymphocyte samples were simultaneously thawed, phytohemagglutinin activated, and analyzed for benz(a)anthracene-induced aryl hydrocarbon hydroxylase (AHH) levels, [3H]thymidine incorporation, and reduced nicotinamide adenine dinucleotide-dependent cytochrome b5 (cytochrome c) reductase activity. Determinations were made at both 96 and 120 hr in culture, and peak activities were compared among a total of 51 individuals who expressed such lesions as squamous cell carcinomas (22%), adenocarcinomas (14%), oat cell carcinomas (6%), chronic obstructive pulmonary disease (22%), and other nonmalignant diseases. Of the 14 highest AHH/cytochrome c activities observed, all were found in patients with primary lung cancer. Mean AHH/cytochrome c activities were 0.89 for lung cancer patients (a total of 21) and 0.47 for noncancer patients (a total of 30) (p less than 0.001). No relationship was observed between AHH/cytochrome c activity and age of patient, numbers of cigarettes smoked, family history of cancer, location or histological type of tumor, or level of phytohemagglutinin blastogenesis ([3H]thymidine cpm/cytochrome c). Whether the higher AHH levels are the cause or the result of the primary lung cancer remains to be determined.
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PMID:Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. 629 46

Studies were conducted to examine the insulin and proinsulin synthetic response to glucose in the streptozotocin-nicotinamide--induced rat islet adenoma. Tumors responded to an increase from 3.8 mmol/L to 16.6 mmol/L glucose by increasing incorporation of [3H]-L-leucine into both proinsulin and insulin. Though this response was statistically significant, the stimulation was less than that noted in rat islets, and the variability of incorporation was greater. In addition, the conversion of proinsulin to insulin was generally slow, again with substantial intertumor variation. The recovery of insulin, as well as proinsulin, was significantly higher at the end of four hours of incubation in tumors incubated in 16.6 mmol/L glucose, implicating an insulin-degradative pathway modulated by glucose. Therefore, while the tumor will not replace conventional sources of tissue for insulin biosynthetic experiments, systems utilizing the tumor can serve as an addition to the methodology for studying previously unrecognized or poorly understood intracellular processes within the beta cell.
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PMID:The effect of glucose on insulin and proinsulin synthesis in the streptozotocin-nicotinamide--induced rat islet adenoma. 631 16

Preliminary studies were conducted to develop a cell-free system for insulin biosynthesis using the streptozotocin-nicotinamide--induced rat islet adenoma. Radiolabeled proteins, migrating on steric exclusion chromatography and SDS-gel electrophoresis in the region of insulin and proinsulin, were synthesized in a system prepared from the tumor 800 X g supernatant fraction, rat liver cytosol, and appropriate energy substrates. The proteins were not synthesized by a rat liver cell-free system, and synthesis could be substantially inhibited by the addition of cycloheximide. In addition, it could be shown that the islet proteins were not the products of residual intact cells within the system, nor were they an artifact due to nonspecific binding of [3H]-L-leucine to pre-existing insulin and proinsulin. The radiolabeled material eluting with insulin on steric exclusion chromatography was identified as [3H]-insulin by immunoaffinity column chromatography.
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PMID:The synthesis of insulin and proinsulin in a cell-free system derived from the streptozotocin-nicotinamide--induced rat islet adenoma. 631 18

Pancreatic exocrine and endocrine function in the rat with islet cell tumors induced by streptozotocin and nicotinamide was studied in the in vitro isolated perfused pancreas. The tumor-bearing pancreas secreted significant amounts of insulin even at 2.8 mM glucose stimulation. Further, insulin response to 8.3 mM glucose stimulation was greater in the tumor-bearing pancreas than in the control. Not only endocrine, but also exocrine, disorders were found in the rat pancreas bearing islet cell tumors. In contrast to the increased response of insulin, amylase output in response to 0.1 ng/ml cerulein was significantly lower in the tumor-bearing than in the control pancreas, although there was no difference in pancreatic juice flows from both groups. These results suggest that enzyme secretory function of the pancreas with islet cell tumors may be suppressed in the presence of some interrelationship between the exocrine and endocrine portion of the pancreas with islet cell tumors.
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PMID:Exocrine and endocrine secretion from isolated perfused rat pancreas with islet cell tumors induced by streptozotocin and nicotinamide. 632 6

Effects of adenosine and related compounds on the regulation of steroid production by isolated Leydig cells have been investigated. Steroid production by freshly isolated Leydig cells from testes of immature or mature rats and mice, or from Leydig tumor tissue could not be stimulated with adenosine, nicotinamide-adenine dinucleotide (phosphate) [NADPH, NAD(P)] or N6-(1-2-phenylisopropyl)-adenosine (PIA) (50 microM), whereas luteinizing hormone (LH) stimulated steroid production more than 10-fold. After 24 h incubation all adenosine-related compounds, but not inosine, stimulated steroid production to 20-100% of the maximal LH-stimulated activity. LH- or 22R -hydroxycholesterol-stimulated steroidogenesis in Leydig cells from immature rats did not decrease during the 24-h culture period, whereas ATP levels increased. The first significant effect of adenosine on steroid production in these cells was found after an incubation period of 3 h. In cells incubated for 1 h and 24 h, LH stimulated cyclic adenosine 3':5'-monophosphoric acid (cAMP) production 10-fold. Significant effects of adenosine and PIA on cAMP production or protein phosphorylation could only be shown in cells incubated for 24 h. Effects of adenosine on Leydig cells in intact testis tissue of immature rats could not be determined. The results suggest that after isolation of Leydig cells, specific alterations in the cell membrane occur, causing increased sensitivity to adenosine and related compounds. Adenosine apparently does not play a role in the role of steroid production in Leydig cells in vivo.
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PMID:Development of adenosine responsiveness after isolation of Leydig cells. 632 34

14C-Nicotinic acid (NA) incorporation into nicotinamide adenine dinucleotide (NAD) was studied in cultures from 7 normal human pituitaries and 13 chromophobe adenomas. 14C-NA (7.2 microM) was incubated with both normal and tumor cell cultures for periods up to 48 hours. Cells and culture media were examined separately for metabolites at 24 and 48 hours. NAD was the major labeled metabolite found in both normal and tumor cells, accounting for 65.4% for normal cells and 56.8% for tumor cells of the total cellular label at 48 hours. Nicotinamide (NAm), a product arising from NAD, was the only labeled metabolite found in the culture medium, aside from the 14C-NA added initially. Total incorporation of 14C-NA into NAD was estimated by adding the cellular 14C-NAD and labeled products of NAD (NMN, NAm and NADP) to the 14C-NAm found in the medium for each culture. Cultures derived from adenomas demonstrated greater than twice the rate of incorporation of 14C-NA into NAD as did normal cell cultures (P less than 0.01 at 24 hours and less than 0.001 at 48 hours). This difference did not appear to be related to the secretory status of the tumor, since both secreting and nonsecreting tumors demonstrated increased rates when compared to normal cells. This difference also persisted in two different culture media and with cells that had been maintained in culture for different lengths of time (6-day dispersed cell cultures and 6- to 16-week fragment cultures).
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PMID:Pyridine nucleotide synthesis in normal and neoplastic human pituitary cells in culture. 635 24

The P-450 cytochromes, reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase, epoxide hydrolase, and glutathione S-transferases all play important roles in the bioactivation and detoxication of various classes of chemical mutagens and carcinogens. The present investigation was undertaken to determine if and where these enzymes are located within the exocrine pancreas, a tissue that is a target for chemically induced neoplasia. In this study, reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase, two isozymes of cytochrome P-450 (cytochromes P-450 PB-B and BNF-B), epoxide hydrolase, and glutathione S-transferases B, C/A, and E were each localized at the light microscopic level within exocrine pancreases of untreated rats and hamsters utilizing the unlabeled antibody peroxidase-antiperoxidase staining technique. Immunohistochemical staining for each of these enzymes was apparent within acinar cells in pancreases of Holtzman, Sprague-Dawley, Wistar, and Fischer 344 rats. Staining for the reductase, the epoxide hydrolase, and the glutathione S-transferases was also observed within the epithelia of both interlobular and intralobular ducts in the exocrine pancreases of these rat strains, whereas staining for cytochromes P-450 PB-B and BNF-B was not readily detectable within epithelial cells of the rat pancreatic duct system. In the exocrine pancreas of the Syrian golden hamster, immunohistochemical staining for reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase, epoxide hydrolase, and glutathione S-transferases B and C/A was similar to that observed within the rat exocrine pancreas. In contrast, acinar and duct cells in the hamster pancreas both appeared to be stained for cytochrome P-450 PB-B, whereas staining for cytochrome P-450 BNF-B could not be readily detected within either acinar or duct cells, and staining for glutathione S-transferases E did not appear to be present within duct cells in the hamster pancreas. The results of this investigation therefore suggest that highly reactive and toxic electrophilic metabolites of procarcinogens may be generated to the greatest extent within acinar cells in the rat pancreas, whereas these metabolites may be produced within both acinar and duct cells in the hamster pancreas. Regardless of where they are formed, reactive metabolites may be enzymatically detoxicated within both acinar and duct cells in the rat and hamster exocrine pancreas.
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PMID:Immunohistochemical localization of carcinogen-metabolizing enzymes within the rat and hamster exocrine pancreas. 641 77


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