Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin, proinsulin, glucagon and gastrin were determined in extracts of tumors of 27 patients with pancreatic islet cell neoplasia of pancreas, in one patient with nesidioblastosis, in extracts of uninvolved portions of the pancreas in 11 of the tumor patients and of 15 control pancreases. Mean insulin concentration in solitary adenomas and in adenomas of patients with adenomatosis was higher than in control pancreases; however, in all but 1 patient the insulin concentration in neoplastic islet tissue was lower than in islet tissue of control pancreas, assuming islet volume is 1% of pancreas. The percentage of proinsulin was elevated in 52% of tumors. Adenoma insulin content correlated with increments of plasma insulin after tolbutamide administration. Insulin and proinsulin concentrations in pancreas uninvolved by tumor were not suppressed. Fasting plasma glucagon was elevated in patients with islet cell adenomatosis and in patients with islet cell carcinoma some of whom had multiple endocrine adenomatosis. The mean concentration of glucagon in tumors was lower than in control pancreases. Elevated concentration of gastrin was found in some adenomas. The data indicate: 1) insulin-secreting islet cell tumors have decreased storage capacity for insulin, 2) elevated concentration of proinsulin in tumors may be due to decreased capacity to store insulin and in some to decreased conversion of proinsulin to insulin as well, 3) tolbutamide stimulates the exaggerated release of a relatively constant fraction of insulin stored in adenomas. 4) solitary adenomas may contain excess amounts of pancreatic hormones in addition to insulin, 5) elevated plasma glucagon in patients with organic hyperinsulinism may indicate malignancy, microadenomatosis or multiple endocrine adenoma syndrome, and 6) chronic hyperinsulinism and hypoglycemia due to adenoma do not suppress insulin and proinsulin content of uninvolved pancreas.
 ...
PMID:Insulin, proinsulin, glucagon and gastrin in pancreatic tumors and in plasma of patients with organic hyperinsulinism. 1 70

Cell cultures were established from a benign pancreatic islet adenoma. Over 200 muU/culture/day immunoreactive insulin were found in culture media. Cultures with medium 199 released insulin for about 2 months; those with medium F12K were maintained for over 7 months, and have been successfully subcultured. Increasing culture medium glucose to 326 mg per 100 ml, alone or with leucine (10 mM) or theophylline (2 mM), failed to increase insulin release above baseline. Studies in the patient prior to surgery using oral glucose, leucine, beef meal, intravenous tolbutamide, and glucagon failed to increase plasma insulin and thus were consistent with cell culture responses. Extracts of tumor tissue contained 23% proinsulin-like material; high insulin containing samples of culture medium had 5% proinsulin and less than 40 pg glucagon/ml. Aldehyde fuchsin positive granulation was sparse in both cultured cells and the original tumor. These studies demonstrate long term viability, in monolayer culture, of cells derived from this islet cell adenoma, with retention of secretory characteristics consistent with data obtained prior to removal of the adenoma from the patient.
 ...
PMID:Human islet cell adenoma: metabolic analysis of the patient and of tumor cells in monolayer culture. 17 12

A 56-year-old woman with symptoms of weakness, visual blurring, and sweating underwent diagnostic studies to evaluate the etiology of her hypoglycemia. Fasting hypoglycemia was never documented; in diagnostic studies performed during her two hospitalizations and several outpatient glucose tolerance tests, the lowest fasting plasma glucose recorded was 56 mg/dl. The patient displayed exaggerated plasma insulin responses following oral glucose (peak response: 447 muU/ml at 30 min) and following 1 gm of iv tolbutamide (peak response: 719 muU/ml at 5 min) with symptomatic profound hypoglyceria during both tests. Basal per cent proinsulin was elevated at 49% (normal range 5-22%). Throughout a 72 h fast, values for plasma glucose, insulin, and glucose/insulin ratios were all within the normal range. During the infusion of exogenous insulin (0.1 U/kg for 60 min) serum C-peptide reactivity suppressed to less than 1.3 ng/ml when the plasma glucose fell below 40 mg/dl representing normal suppression. At surgery, a pancreatic beta cell adenoma was found and removed. This patient represents the uncommon circumstances in which stimulation tests with tolbutamide and glucose were more helpful in establishing a preoperative diagnosis than were the suppression tests.
 ...
PMID:Nonautonomous function of a pancreatic insulinoma. 18 13

The regulation of insulin biosynthesis, and insulin and glucagon secretion have been investigated in a human islet cell adenoma, by incubation of tumour fragments. Both biosynthesis and secretion of insulin were strongly stimulated by incubation of islet tumour cells in the presence of increasing glucose concentrations in the range 2-8 mmol/1. However, 20 mM-glucose or 20 mM-glucose plus isobutyl methylxanthine (IBMX), both of which provide potent secretagogues for normal B cells, failed to stimulate proinsulin biosynthesis and secretion from the tumour cells. Overall rates of secretion, expressed as a proportion of total insulin content, were up to 20-fold higher than those expected for normal pancreatic tissue. Glucagon secretion from the tumour was stimulated by low glucose concentrations; normal A cells also respond in this way under these conditions. However, no stimulation of glucagon secretion occurred in the presence of IBMX. There was therefore a major alteration in the regulation both of insulin and glucagon secretion, in that release of neither hormone was stimulated by cyclic AMP. Ultrastructural examination showed the tumour to be rather heterogeneous. A and B cells with normal storage granule content and structure were seen, as well as a rather larger number of B cells containing some granules of atypical appearance. The insulin content of the tumour (13 i.u./g wet wt) was consistent with 6-8% of the tumour cells being B cells.
 ...
PMID:Regulation of insulin and glucagon secretion from a human islet cell adenoma. 19 89

To examine possible feedback inhibition of insulin on proinsulin secretion, we measured serum proinsulin levels before and after 120 min of euglycemic hyperinsulinemia (90-100 mU/liter) in 11 normal and 7 obese hyperinsulinemic subjects and 6 patients with beta-cell adenoma (n = 4), carcinoma, or hyperplasia. Baseline proinsulin levels accounted for 19%, 14%, and 56% of the total immunoreactive insulin in the 3 groups, respectively. Compared to normal subjects, baseline proinsulin levels were elevated (P less than 0.02) by 4- and 6-fold in obese subjects and patients with autonomous insulin secretion, respectively, but there was an overlap between the groups. In both normal and obese subjects, hyperinsulinemia suppressed proinsulin secretion by 45-50% (P less than 0.02), whereas no response occurred in the patients. Thus, the 120 min values were clearly different in the patients and the normal or obese subjects. After removal of the adenoma in 4 patients, baseline proinsulin levels and the response to hyperinsulinemia were normalized, but they remained elevated after a partial pancreatectomy or tumor removal in the patients with beta-cell hyperplasia or carcinoma. Thus, proinsulin secretion is under negative feedback control of insulin in both normal man and hyperinsulinemic obese subjects. In patients with insulinoma or beta-cell hyperplasia, this control is lost.
 ...
PMID:The effect of exogenous hyperinsulinemia on proinsulin secretion in normal man, obese subjects, and patients with insulinoma. 302 76

Plasma insulin immunoreactivity (IRI) results from high molecular weight substances with insulin immunoreactivity (HWIRI), proinsulin (PI) and insulin (I). Their respective concentrations and percentages of IRI were determined preoperatively in the hepatic and peripheral circulations and after surgery in the latter two and in the portal circulation in a patient with a pancreatic adenoma. Removal of the insulinoma resulted in a highly significant reduction of PI concentration in the hepatic (from 16.2 +/- 1.9 microU/ml to 7.3 +/- 0.8 microU/ml) and in the peripheral (from 24.0 +/- 2.0 microU/ml to 9.2 +/- 1.2 micro U/ml) venous systems. Similarly, I concentration decreased in the hepatic (from 36.9 +/- 3.4 microU/ml to 28.0 +/- 1.0 microU/ml) and peripheral (from 33.8 +/- 3.4 microU/ml to 19.8 +/- 2.0 microU/ml) venous systems. HWIRI concentration decreased in the hepatic venous system (from 6.9 +/- 0.8 microU/ml, to 4.8 +/- 0.6 microU/ml), but the decrease in the peripheral venous system (from 9.7 +/- 1.4 microU/ml to 8.2 +/- 1.2 microU/ml) was not significant. It was found that the concentration of I virtually was the same in hepatic and peripheral blood prior to operation in contrast to a decrease seen after the operation. This indicates that the hyperinsulinemia caused primarily by the autonomous hypersecretion of the insulinoma was amplified by a decreased degradation of insulin by the liver and kidney. Our results also indicate that HWIRI was found with the highest concentration in the peripheral blood independently of the adenoma.
 ...
PMID:Portal, hepatic and peripheral insulin immunoreactive substances before and after removal of an insulinoma. 629 20

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.
 ...
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.
 ...
PMID:The synthesis of insulin and proinsulin in a cell-free system derived from the streptozotocin-nicotinamide--induced rat islet adenoma. 631 18

Plasma concentrations of proinsulin and C-peptide were measured in five children presenting with severe hypoglycaemia associated with elevated plasma levels of immunoreactive insulin (IRI) in order to determine whether the profile of circulating B-cell products related to the underlying pathophysiology of the pancreas. Results were compared with data from 13 normal infants. Four children, three neonates and a nine year old girl, were subjected to partial or total pancreatectomy. The neonates had nesidioblastosis, nesidioblastosis with a microadenoma, and a functional abnormality without histological derangement respectively; the older child had a localised adenoma. The remaining child, a neonate, had transient hypoglycaemia and elevated IRI levels associated with hyperlactataemia and hyperalaninaemia. All the children had markedly elevated plasma proinsulin concentrations; the highest levels were seen in the child with an isolated adenoma and in the neonate with nesidioblastosis and a microadenoma. Both of these children also had substantially elevated plasma C-peptide concentrations. The remaining three neonates had plasma C-peptide levels, which although in the normal range for normoglycaemia were inappropriately elevated during hypoglycaemia. It is concluded that elevated proinsulin and C-peptide concentrations are seen in children with hypoglycaemia associated with increased plasma IRI levels and that the profile of the concentrations does not provide a reliable marker for the nature of the underlying pancreatic abnormality.
 ...
PMID:Plasma proinsulin and C-peptide concentrations in children with hyperinsulinaemic hypoglycaemia. 637 10

Cytogenetic study of short-term cultures from 10 adipose tissue tumors (eight lipomas, one myxoid liposarcoma, and one mixed liposarcoma) have revealed clonal chromosome abnormalities in seven cases. In both malignant tumors, translocation (12;16) was the sole aberration, and in the mixed liposarcoma, the breakpoints could be sublocalized to bands 12q13.3 and 16p11.2, thus confirming findings of Eneroth et al., Cancer Genet. Cytogenet., 48: 101-107, 1990. Three lipomas displayed predominantly normal karyotypes; in a fourth case, the karyotype 44,XX,-6,der (7)t(6;7)(p21.3-22;p22)ins(7)(p22q11.2q22),-13 was found. Four remaining lipomas were characterized by structural rearrangements of chromosome 12. We were able to achieve high resolution banding patterns in two tumors with translocations (3;12)(q28;q15) and (1;2;12)(p36.;q13;q15). In both of these cases, the chromosome 12 breakpoint could be unequivocally assigned to band q15. Similarly, band 12q15 was also rearranged in two other lipomas with translocations (12;14)(q15;q32) and (12;20)(q15;q13.1). Our results support the hypothesis that the chromosome 12 breakpoint in lipomas is located more distally than the breakpoint in myxoid liposarcomas and some other soft-tissue malignant neoplasms and that it is cytogenetically identical with breakpoints detected in such benign tumors as uterine leiomyoma and pleomorphic adenoma of the salivary gland.
 ...
PMID:Chromosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3. 845 40


1 2 3 Next >>