Disease relevance of Insulinoma

• In seven insulinomas and two glucagonomas, we found the somatostatin content either much lower (less than 0.6 ng per milligram of tissue) or undetectable [1].
• VIP scans were positive in 9 of 10 patients with carcinoid tumors and in 4 of 4 patients with insulinomas [2].
• Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma [2].
• For example, as depicted in Fig. 4, episodes of mild hypoglycemia occurring in insulinoma patients, diabetic patients undergoing intensive insulin therapy, or patients with longstanding diabetes complicated by autonomic neuropathy and impaired glucagon secretion could lead to CNS adaptation.(ABSTRACT TRUNCATED AT 400 WORDS)[3]
• Immunohistochemical studies of neuron-specific enolase were performed on pancreatic tissues from patients with insulinoma, nonfunctioning islet cell tumor, chronic pancreatitis, and pancreatic adenocarcinoma, and from 5 normal patients [4].

High impact information on Insulinoma

• We evaluated the role of IBi in beta-cells by expression of a MAPK8IP1 antisense RNA in a stable insulinoma beta-cell line [5].
• High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma [6].
• Letter: Phenytoin in metastatic insulinoma [7].
• Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions and deficient perivascular deposition of ECM components [8].
• In the current study, we show that IL-1beta induces destruction of INS-1 insulinoma cells, while having no effect on a second insulinoma cell line RIN1046-38 and its engineered derivatives, and that this difference is correlated with a higher level of expression of manganese superoxide dismutase (MnSOD) in the latter cells [9].

Chemical compound and disease context of Insulinoma

• Enhanced stimulus-secretion coupling in polyamine-depleted rat insulinoma cells. An effect involving increased cytoplasmic Ca2+, inositol phosphate generation, and phorbol ester sensitivity [10].
• IL-1 beta also induces the accumulation of cGMP by the insulinoma cell line Rin-m5F, and both NMMA as well as the protein synthesis inhibitor cycloheximide prevent this cGMP accumulation [11].
• Glucose-induced hypoglycaemia in insulinoma with impaired glucose tolerance [12].
• Calcium antagonist (diltiazem) for reversal of hypoglycaemic symptoms in insulinoma [13].
• Galanin was also found to abolish glyceraldehyde-stimulated immunoreactive insulin release from the insulinoma cells [14].
• In fresh insulinoma cultures, insulin expression was increased by oestrogen or progesterone, whereas no significant effect was observed in adjacent pancreatic tissue [15].

Biological context of Insulinoma

• A partial amino acid sequence of cat islet IAPP corresponding to positions 1-27 of human insulinoma IAPP was identical to the human IAPP except for substitutions in three positions [16].
• Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in beta TC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene [17].
• The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM) [18].
• INSAF was isolated from a human insulinoma cDNA library [19].
• Ca2+-dependent protein phosphorylation and insulin release in intact hamster insulinoma cells. Inhibition by trifluoperazine [20].

Anatomical context of Insulinoma

• GLUT2 surface expression and intracellular transport via the constitutive pathway in pancreatic beta cells and insulinoma: evidence for a block in trans-Golgi network exit by brefeldin A [21].
• Subcellular fractionation of insulinoma cells showed CSP1 (34/36 kDa) in granular fractions; the membrane and cytosol fractions contained predominantly CSP2 (27 kDa) [22].
• An antiserum raised to a synthetic human insulinoma IAPP-(7-17) undecapeptide showed specific immunohistochemical reactivity with human and cat islet amyloid and with islet B cells [16].
• Localization of inositol trisphosphate receptor subtype 3 to insulin and somatostatin secretory granules and regulation of expression in islets and insulinoma cells [23].
• They were also increased in rat insulinoma RINm5F cells cultured in 25 mM glucose compared with cells cultured in 5 mM glucose [23].

Gene context of Insulinoma

• Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice [24].
• The long form of the leptin receptor (OB-Rb) mRNA was present in the islets and insulinoma cell lines [24].
• SMS 201-995 may also be useful in treating the symptoms in some patients with glucagonomas, growth hormone releasing hormone-producing tumors and insulinomas [25].
• IAPP from human insulinoma contained 37 amino acid residues and had a theoretical molecular mass of 3850 Da [16].
• Islet amyloid polypeptide (IAPP) is a 37-amino acid peptide found in the pancreatic amyloid deposits of type II (non-insulin-dependent) diabetic patients and insulinomas [26].
• Our data are consistent to the possibility that SERPINA1 is a marker of malignancy in insulinomas [27].

Analytical, diagnostic and therapeutic context of Insulinoma

• Northern blot analysis revealed IA-1 mRNA in five of five human insulinoma and three of three murine insulinoma cell lines [28].
• Oligonucleotide microarrays were used to define oleic acid (OA)-regulated gene expression and proteomic technology to screen protein kinases in MIN6 insulinoma cells [29].
• An insulin-degrading enzyme inhibitor decreases amylin degradation, increases amylin-induced cytotoxicity, and increases amyloid formation in insulinoma cell cultures [30].
• Our aim was to identify the isoforms of CaMK II expressed in human beta cells by molecular cloning from a human insulinoma cDNA library and to assess its distribution in humans [31].
• The effect of endogenous hyperinsulinaemia, produced by syngeneic transplantation of rat insulinoma at an extrapancreatic site, on pancreatic insulin and pancreatic polypeptide has been examined by radioimmunoassay and immunohistochemistry [32].

References