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

In the present study we have evaluated the effects of chronic hyperinsulinaemia secondary to insulinoma, on insulin sensitivity and on counter-regulatory responses to hypoglycaemia. We studied six patients (M/F = 3/3; age = 40 +/- years), before and 6-9 months after surgical ablation of the neoplasia, by means of an euglycaemic-hyperinsulinaemic clamp (1 mU kg-1 min-1). Seven normal subjects (M/F = 4/3; age = 38 +/- 6 years) underwent the same experimental study as the control subjects. In insulinoma patients after 100 min of the euglycaemic-hyperinsulinaemic clamp, glycaemia was allowed to drop to a minimum value of 1.9 mmol L-1, and recovery evaluated after interrupting insulin infusion. During the entire study, 3-3H-glucose was infused to determine hepatic glucose production and glucose utilization. Surgical removal of the pancreatic adenoma was followed by a reduction in body weight (BMI = 25.7 +/- 1.9 vs. 23.0 +/- 1.6 kg m-2; P < 0.05), normalization of fasting plasma levels of glucose (2.94 +/- 0.16 vs. 4.83 +/- 0.11 mmol L-1), insulin (162 +/- 24 vs. 48 +/- 12 pmol L-1) and of basal hepatic glucose production (7.6 +/- 0.7 vs. 12.2 +/- 1.11 mumol kg-1 min-1). Before the operation, insulin-mediated glucose disposal was significantly lower than in the controls (30.8 +/- 3.1 vs. 49.1 +/- 3.1 mumol kg-1 min-1). Six to nine months after surgical removal of the adenoma, glucose utilization was unchanged (30.5 +/- 3.3 mumol kg-1 min-1) and still significantly lower than in controls (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Surgical removal of insulinoma restores glucose recovery from hypoglycaemia but does not normalize insulin action. 762 24

Surgical material from 51 patients operated on for insulinoma is studied. Three histological variants of insulinoma are distinguished: adenoma-like, insular-ductal and carcinoid-like. The structure of Langerhans islands outside the tumour is described and the diagnostic criteria of insuloma-microadenoma are presented. Multiple nests of the endocrine cells are regarded either as a manifestation of the multifocal island pathology or as a marker of non-diagnosed insuloma. There is a need of distinguishing between the terms related to the nosology and histogenesis of endocrine pancreatic tumours.
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PMID:[A retrospective clinico-morphologic study of insulinoma]. 767 78

Somatostatin (SRIF) exerts its diverse biological effects through a family of membrane receptors. In addition to inhibiting GH secretion, SRIF has antiproliferative effects and has been used clinically in the treatment of pituitary tumors. SRIF receptor (SSTR) expression has recently been identified in pituitary adenomas, and it is unknown whether differential expression of SSTR subtypes predicts clinical responses to SRIF analogs. We therefore determined which SSTR subtype messenger RNAs (mRNAs) are expressed in pituitary adenoma phenotypes and in normal human pituitary tissue using reverse transcriptase-polymerase chain reaction and tested whether expression of specific SSTR subtype mRNA is necessary for SRIF inhibition of GH secretion in human somatotroph adenomas in vitro. Expression of SSTR subtypes 1, 2, and 5 mRNA was identified in all pituitary adenoma types and normal pituitary tissue. In contrast, SSTR3 mRNA was detected in only one somatotroph adenoma as well as in control insulinoma tissue, a tissue known to express SSTR3 mRNA, and was not detected in normal pituitary tissue. SSTR4 mRNA was not detected in any human pituitary tissue. To determine whether specific SSTR subtype mRNA expression is required for SRIF inhibition of GH secretion, five somatotroph adenomas were treated with 10(-7) mol/L SRIF in vitro, and significant inhibition of GH release occurred in all adenomas. All five tumors expressed SSTR2 mRNA and SSTR5 mRNA, and three expressed SSTR1 mRNA. The absence of SSTR1 mRNA expression did not affect the ability of SRIF to suppress GH secretion. We conclude that: 1) human pituitary adenomas and normal pituitary express multiple SSTR gene transcripts; 2) SSTR5 mRNA, which has not been reported in other human endocrine tumor types, is expressed in neoplastic and normal pituitary tissue; and 3) SSTR2 mRNA, SSTR5 mRNA, and variable SSTR1 mRNA are expressed in GH-secreting tumors, which are responsive to SRIF in vitro. Further understanding of SSTR gene expression in pituitary adenomas will facilitate our understanding of the pathogenetic mechanisms of tumorigenesis and may provide a rationale for the use of specific SRIF analogs for clinical application.
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PMID:Somatostatin receptor subtype gene expression in pituitary adenomas. 771 15

Using a combination of polymerase chain reaction and genomic library screening we have cloned a human gene for a subtype of the somatostatin (SST) receptor (SSTR) termed human SSTR5 (hSSTR5), which is located on chromosome 16. The predicted amino acid sequence of hSSTR5 displays 75% sequence identity with a recently identified rat SSTR [Mol. Pharmacol. 42:939-946 (1992)], suggesting that it is the human homologue of this receptor. hSSTR5 consists of a 363-residue polypeptide exhibiting a putative seven-transmembrane domain topology typical of G protein-coupled receptors. The receptor displays considerable sequence identity to hSSTR1 (42%), hSSTR2 (48%), hSSTR3 (47%), and hSSTR4 (46%). Membranes prepared from COS-7 cells transiently expressing the hSSTR5 gene bound 125I-Leu8,D-Trp22,Tyr25-SST-28 (125I-LTT-SST-28) with high affinity and in a saturable manner. SST-14, SST-28, and various synthetic SST peptide agonists produced dose-dependent inhibition of radioligand binding with the following rank order of potency: LTT-SST-28 > SST-28 > D-Trp8-SST-14 > SST-14 approximately RC-160 approximately BIM 23014 > MK-678 > SMS 201-995. hSSTR5 bound SST-28 with a 12.6-fold greater affinity (Ki = 0.19 nM), compared with SST-14 (Ki = 2.24 nM), indicating that the receptor is SST-28 selective. Addition of GTP, guanosine-5'-O-(3-thio)triphosphate, Na+ ions, or pertusis toxin greatly reduced 125I-LTT-SST-28 binding, thereby indicating that hSSTR5 is coupled to pertussis toxin-sensitive G proteins. Both SST-14 and SST-28 displayed dose-dependent inhibition of forskolin-stimulated cAMP accumulation, consistent with functional coupling of the receptor to adenylyl cyclase inhibition. Northern blot analysis of SSTR5 mRNA revealed a 2.4-kilobase transcript in normal rat pituitary and GH3 rat pituitary tumor cells and a 4.0-kilobase transcript in normal human pituitary. Reverse transcriptase polymerase chain reaction revealed expression of the hSSTR gene in fetal human pituitary and hypothalamus but not in human cerebral cortex. In situ hybridization of the rat pituitary showed that SSTR5 mRNA is selectively localized in the anterior lobe. SSTR5 mRNA was not expressed in four human pituitary tumors (somatotroph adenoma, prolactinoma, and chromophobe adenomas) or in a human insulinoma. Although hSSTR5 displays approximately 75% sequence identity with rat SSTR5, the two receptors display significantly different pharmacological profiles, especially with respect to their binding affinities for the SST analogue SMS 201-995.
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PMID:Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28. 790 5

Hyperinsulinaemia due to pancreatic beta-cell tumours has been reported to lead to insulin resistance. A possible contribution of dysregulated insulin receptors to the impaired insulin action of insulinoma has not been explored. Therefore, we studied insulin receptor function in a patient with insulin-producing adenoma. This patient was rather unusual in that she was found to have a very large tumour and strikingly high circulating levels of insulin. In addition, her previous history included type 2 (non-insulin-dependent) diabetes mellitus. We confirmed decreased glucose utilization and metabolic clearance rate for glucose in presence of marked endogenous hyperinsulinaemia (approximately 2000 pM). 125I-labelled insulin binding capacity and receptor affinity for insulin were normal in her intact blood monocytes and erythrocytes. Insulin receptors were purified from the patient's tumour as well as from the pancreas, omental fat, liver and erythrocytes. All parameters of insulin binding to these receptors were normal. Thus, no evidence of receptor downregulation due to the marked hyperinsulinaemia was found. As expected, addition of insulin in vitro stimulated receptor autophosphorylation and tyrosine kinase activity of the receptors isolated from the liver, fat and erythrocytes. However, the basal tyrosine kinase activities of the tumour and pancreatic receptors were very high when isolated and further addition of insulin in vitro increased the protein kinase activity only slightly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin resistance in a case of coexisting insulinoma and type 2 diabetes. 818 Apr 17

The rodent SSTR2 mRNA has been reported to be alternatively spliced to generate long (SSTR2A) and short (SSTR2B) receptor isoforms which differ in sequence at their C-terminal regulatory domains. By extending the 3' nucleotide sequence of the human gene (hSSTR2) we show highly conserved intron/exon boundaries suggesting that hSSTR2 is also capable of generating spliced variants. mRNA blots of rat tissues reveal 2 transcripts of 2.8 and 2.3 kb that are differentially expressed in brain regions and multiple peripheral organs. The 2.3 kb mRNA is preferentially expressed in pituitary tumor cells (AtT-20 mouse, GH3 rat, human prolactinoma, human somatotroph adenoma), but not in rat or human insulinoma cells. This transcript shows 4 fold induction by forskolin in AtT-20 cells suggesting cAMP dependent control of SSTR2 gene expression. The abundant expression of SSTR2 gene, the occurrence of 2 isoforms and evidence of extensive regulation at both gene and peptide levels, suggests that SSTR2 is the principal SST-14 selective subtype.
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PMID:Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation. 838 8

We report a series of 30 patients with pancreatic insulinoma treated from 1967 to 1990. Twenty-nine patients underwent surgery. In 24 patients, the lesion was a benign adenoma. The pancreatic lesion was localized preoperatively in 59% of cases (94% since 1980), and all lesions that were identifiable histologically were palpable intraoperatively. Endoscopic pancreatic ultrasonography, performed twice, appeared to be a very promising method of investigation. In the 24 patients with adenoma, 14 enucleations and 10 pancreatic resections were performed, with the enucleation rate increasing over time. One patient died during the postoperative period. Pancreatic fistulas (43%) were the most common cause of morbidity and were more common after enucleation (57% versus 29% after pancreatectomy). The mean follow-up period was 7 years. Excluding the patients with adenocarcinomas, the recovery rate was 92% (23 of 25 among whom 2 patients had transitory recurrent hypoglycemia), 2 patients who underwent corporeo-caudal pancreatectomy being diabetic (8%).
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PMID:Pancreatic insulinomas. 842 5

To gain further insight into the pathogenesis of fasting hypoglycemia in patients with insulin-secreting adenoma of the pancreas, we studied seven patients affected by insulinoma (age, 42 +/- 7 years; body mass index [BMI], 27 +/- 2 kg/m2) and seven normal subjects. In insulinoma patients, hepatic glucose production (HGP) and glucose utilization (Rd) were evaluated by infusion of 3-3H-glucose at spontaneous fasting plasma glucose concentration, after restoration of euglycemia and during euglycemic insulin clamp (40 mU/m2/min). In insulinoma patients, fasting plasma glucose concentration (2.8 +/- 0.2 v 4.5 +/- 0.1 mmol/L; P < .001), HGP, and glucose Rd (7.8 +/- 1.1 v 12.0 +/- 0.3 mumol/kg/min; P < .01) were lower than in normal subjects, while plasma insulin level was higher (138 +/- 19 v 38 +/- 3 pmol/L; P < .001). In insulinoma patients after attainment of euglycemia (4.7 +/- 0.2 mmol/L) by exogenous glucose infusion, insulin level increased slightly (174 +/- 18 pmol/L; P < .01) and glucose Rd was similar to that of normal individuals (12.8 +/- 0.6 v 12.0 +/- 0.3 mumol/kg/min). During the clamp studies, glucose Rd was lower in insulinoma patients (18.7 +/- 1.2 v 33.8 +/- 3.1 mumol/kg/min; P < .01) despite higher plasma insulin concentration (612 +/- 48 v 420 +/- 12 pmol/L). Therefore, glucose Rd/I x 100 ratio (where I is plasma insulin concentration) was much lower in insulinoma patients (3.1 +/- 0.9 v 8.0 +/- 0.7; P < .01), suggesting a marked degree of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of fasting hypoglycemia and concomitant insulin resistance in insulinoma patients. 844 44

We describe an immunoluminometric assay (ILMA) for determination of intact proinsulin and its conversion intermediates. 32,33-split and 65,66-split proinsulin, in human serum. After incubation of the serum samples with the IgG fraction of a guinea pig antiserum against human insulin coated to the surface of polystyrene beads, a sandwich complex was formed using a monoclonal antibody against human C-peptide labelled with acridinium ester as second antibody, yielding a detection limit of 0.11 pmol/l. Mean proinsulin concentration in the serum of 38 healthy fasting subjects was 7.3 pmol/l (S.D. +/- 5 pmol/l, median 5 pmol/l, 95th percentile 15 pmol/l); maximum serum proinsulin after oral glucose stimulation never exceeded 40 pmol/l. Eighteen of 20 patients with confirmed insulinoma had proinsulin concentrations over 50 pmol/l (mean 261 pmol/l, S.D. +/- 248 pmol/l, median 170 pmol/l, 95th percentile 663 pmol/l); serum proinsulin in two patients with completely enucleated B-cell adenoma declined to normal values after surgery.
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PMID:Immunoluminometric assay (ILMA) for intact human proinsulin and its conversion intermediates. 892 Feb 24

Since December 1993, in the 1st Nuclear Medicine Service of the University of Padua, eleven somatostatin-receptor scintigraphic studies with 111In-labelled pentetreotide have been performed. The patients (6 men and 5 women, age 28-68, mean 45 years) were affected by a variety of tumors which supposedly express somatostatin receptors: 2 meningotheliomatous meningiomas post-surgery; 2 glucagonomas with liver metastases observed on CT; 2 patients with suspicion of insulinoma; 2 carcinoids, one after surgery; 1 ectopic-ACTH Cushing's syndrome; 1 intracranial germinoma, post-surgery, in whom the study was requested to evaluate a doubtful finding of pulmonary metastatic lesion on CT; and 1 acromegaly showing, on MRI, and empty sella turcica occupied by and extraflexion of the lower portion of the chiasmatic cisterna without signs of adenoma and the sphenoidal sinus occupied by tissue wit inflammmatory characteristics. Somatostatin-receptor whole body scintigraphy was performed 4 and 24 hours after intravenous injection of 110 MBq 111In-pentetreotide (Octreoscan 111); spot images were acquired when judged necessary. In one case of glucagonoma, a tomographic scan (SPECT) was also performed to better evaluate the spatial relationship between the primitive pancreatic tumor and surrounding tissues. Focal accumulation of 111In-pentetreotide was scintigraphically detected in 5 of the 11 cases. Intense uptake of the radiopharmaceutical was observed in the meningiomas, in the glucagonomas with liver metastases, and in the case of acromegaly, corresponding to a GH-secreting adenoma. The negative scans seem to be true negative scans with the possible exception of one patient with a still unconfirmed suspicion of insulinoma, still not confirmed.
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PMID:Whole body and tomographic scan with 111In-pentetreotide: preliminary data. 900 69


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