Disease relevance of Islets of Langerhans

• Inhibition of glucose transport into rat islet cells by immunoglobulins from patients with new-onset insulin-dependent diabetes mellitus [1].
• We measured the uptake of 3-O-methyl-beta-D-glucose by dispersed islet cells from rats after a 15-minute incubation with purified IgG from 27 patients with newly diagnosed IDDM, 28 normal subjects, and 5 patients with non-insulin-dependent diabetes mellitus (NIDDM) [1].
• Type 1, or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease associated with loss of tolerance to several pancreatic islet cell molecules, including insulin, glutamic acid decarboxylase (GAD), ICA69 and the tyrosine phosphatase IA-2 (refs 1-3) [2].
• "Somatostatinoma": a somatostatin-containing tumor of the endocrine pancreas [3].
• Two patients with pancreatic cholera and islet-cell carcinoma were treated with intra-arterial streptozotocin [4].

Psychiatry related information on Islets of Langerhans

• In view of the fact that the beta-amyloid protein that forms fibrils in Alzheimer's disease is toxic to neurons, we have investigated whether amylin fibrils could be toxic to pancreatic islet cells [5].
• These observations suggest that enhancing antioxidant defense mechanisms in pancreatic islets may be a valuable pharmacologic approach to managing diabetes [6].

High impact information on Islets of Langerhans

• Anomeric specificity of hexose metabolism in pancreatic islets [7].
• Expression of a long ENPP1 mRNA isoform, which includes the obesity-associated A-->G+1044TGA SNP, was specific for pancreatic islet beta cells, adipocytes and liver [8].
• Elevations in circulating glucose and gut hormones during feeding promote pancreatic islet cell viability in part via the calcium- and cAMP-dependent activation of the transcription factor CREB [9].
• Pancreatic islets produce Igf1 and Igf2, which bind to specific receptors on beta-cells [10].
• Pbx1+/- adults had pancreatic islet malformations, impaired glucose tolerance and hypoinsulinemia [11].

Chemical compound and disease context of Islets of Langerhans

• Diarrhea in a patient with pancreatic cholera syndrome caused by a vasoactive intestinal polypeptide producing pancreatic islet-cell carcinoma responded rapidly and dramatically to the phenothiazine trifluoperazine [12].
• Among the 14 rats given a single i.p. injection of nicotinamide, 500 mg/kg of body weight, 15 min before a single i.v. injection of streptozotocin, 65 mg/kg of body weight, 13 rats (95%) developed pancreatic islet cell tumors [13].
• PURPOSE: A phase II trial that used fluorouracil (5-FU) and chlorozotocin (CTZ) was performed in patients with metastatic islet cell carcinoma to determine the response rate and toxicity [14].
• Group 4 antibodies (PF4/A, an IgG2a; and PF4/B, an IgG1) are less specific than those of the preceding groups, as they react with some normal tissues, including pancreatic islets and pneumocytes, as well as with a variety of adenocarcinomas and tumors of neuroectodermal origin [15].
• The gamma-aminobutyric acid (GABA) concentration of pancreatic islets in rats treated with streptozotocin (STZ) and of human insulinoma tissue was studied [16].

Biological context of Islets of Langerhans

• No differences were observed between the two groups of patients in age, sex, HLA phenotype, autoantibodies to insulin or islet-cell antigens, or doses or trough levels of cyclosporine [17].
• Proliferation, senescence, and neoplastic progression of beta cells in hyperplasic pancreatic islets [18].
• Destruction of islet cells with streptozotocin in mice induced hyperglycemia, intravascular oxidant production, DNA strand breakage, PARP activation and a selective loss of endothelium-dependent vasodilation [19].
• The LIM homeodomain protein ISL1 is expressed in all classes of islet cells in the adult and its expression in the embryo is initiated soon after the islet cells have left the cell cycle [20].
• B7-1 transgene expression on the pancreatic islets in nonobese diabetic (NOD) mice leads to accelerated diabetes, with >50% of animals developing diabetes before 12 wk of age [21].

Anatomical context of Islets of Langerhans

• When beta cells were lacking in islet-cell tumors or in the pancreas of a patient with juvenile-onset diabetes, kallikrein antigen was not detectable [22].
• Prompted by the recent demonstration of somatostatin in D cells of pancreatic islets, we analyzed the tumor and found a large quantity of immunoreactive somatostatin (301 ng per milligram of tissue) [3].
• Insulin-dependent diabetes mellitus is characterized by the infiltration of lymphocytes into the islets of Langerhans of the pancreas (insulitis) followed by destruction of insulin-secreting beta-cells leading to overt diabetes [23].
• Ca2+-activated ATPase and ATP-dependent calmodulin-stimulated Ca2+ transport in islet cell plasma membrane [24].
• The results suggest that glucose-induced proinsulin synthesis is mainly achieved by enhancing the trnaslation efficiency of proinsulin mRNA preexistent on the membrane-bound polysome in pancreatic islets [25].

Associations of Islets of Langerhans with chemical compounds

• In contrast, the uptake of L-leucine by islet cells was not affected by any of the IgG fractions [1].
• The combination of streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma [26].
• The combination of streptozocin and doxorubicin is superior to the current standard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma [26].
• Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma [26].
• Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets [27].

Gene context of Islets of Langerhans

• Our findings suggest that deficient binding of NEUROD1 or binding of a transcriptionally inactive NEUROD1 polypeptide to target promoters in pancreatic islets leads to the development of type 2 diabetes in humans [28].
• During mouse development, the dorsal and ventral pancreatic buds and mature beta-cells in the islets of Langerhans express Hlxb9 [29].
• In addition, we detected MAPK8IP1 transcripts and IBi protein in human pancreatic islets [30].
• Here we show that inhibition of the activity of cyclin-dependent kinase 5 (Cdk5) enhanced insulin secretion under conditions of stimulation by high glucose but not low glucose in MIN6 cells and pancreatic islets [31].
• The channel, called BIR (Kir6.2), was expressed in large amounts in rat pancreatic islets and glucose-responsive insulin-secreting cell lines [32].

Analytical, diagnostic and therapeutic context of Islets of Langerhans

• Immunofluorescence revealed an islet-cell cytoplasmic antibody (ICA) in 20 patients with IDDM and an islet-cell-surface antibody (ICSA) in 23 [33].
• We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan catabolism in the host [34].
• Adoptive transfer of CD8(+) T cells from influenza hemagglutinin-specific Clone 4 TCR transgenic mice into mice that express hemagluttinin in the pancreatic islets results in tolerance [35].
• Immunocytochemistry revealed that, although pancreatic islet cells in the STZ-treated rats were sparse and atrophic PC1, PC2, glucagon, and GLP-1 immunoreactivity increased dramatically in the remaining islet cells [36].
• Here we describe the regulation of the expression of IDX-1, C/EBPbeta, and insulin at the mRNA and protein levels in pancreatic islets in animal models of diabetes mellitus [37].

References