Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.
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PMID:Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus. 138 78

Insulin-dependent diabetes mellitus (IDDM) in humans and mouse models is caused by a T cell-mediated destruction of the beta cells in the islets of Langerhans. The interaction between T cells and their antigens or targets is assisted by adhesion molecules on the surfaces of lymphocytes and counterreceptors on antigen-presenting or other cells. One such pair of molecules thought to be of importance in IDDM is lymphocyte function-related antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) because culture of islet cells with cytokines results in the expression of ICAM-1 on islet cells in vitro. To understand the importance of this interaction in the development of autoimmune diabetes, we have studied the ability of monoclonal antibodies (mAbs) against LFA-1 and/or ICAM-1 to prevent disease in multidose streptozotocin-induced diabetes mellitus (MDSDM). Treatment with both anti-LFA-1 and anti-ICAM-1 mAbs reduced the development of hyperglycemia and insulitis in this model. Treatment with the anti-LFA-1 and anti-ICAM-1 mAbs caused modulation of LFA-1 and ICAM-1 expression on splenocytes, respectively. In mice that were undergoing streptozotocin-induced diabetes, ICAM-1 was found on capillary endothelial cells and on cells surrounding the islets but was not expressed at detectable levels on islet endocrine cells. Thus, interaction between ICAM-1 and LFA-1 is involved in the development of autoimmune diabetes in MDSDM. It is unlikely that ICAM-1 molecules mediate adherence between T cells and islet cells themselves. Our results suggest that treatment with anti-ICAM-1 and anti-LFA-1 mAbs prevents localization of T cells to the islets rather than causing functional impairments of the lymphocytes. The actual sites of interaction between the T cells involved in MDSDM and ICAM-1 are unknown, but may occur on cells that normally express ICAM-1 in the islet or may occur outside the islet itself.
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PMID:Prevention of autoimmune diabetes by treatment with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies. 791 4

The adhesion of leucocytes to the endothelium, an early step in atherogenesis, is mediated by cell adhesion molecules. In this study we evaluated the concentration of soluble adhesion molecules in patients with insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) and studied its relation to glycaemic control. Soluble adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were measured in 31 diabetic patients (18 with IDDM and 13 with NIDDM), 20 hyperlipoproteinaemic patients (10 with type IIa and 10 with type IIb) and 20 healthy subjects. Increased E-selectin concentrations were found in the patients with IDDM and NIDDM and in the hyperlipoproteinaemic patients when compared to the control subjects (p < 0.01 for all the groups). ICAM-1 was found to be elevated only in the patients with NIDDM (p < 0.01). No significant differences in VCAM-1 concentration were found in the different groups of subjects. The concentration of plasma E-selectin was positively correlated with the glycated haemoglobin (r = 0.54, p < 0.01) in patients with IDDM and NIDDM. In the same patients E-selectin was not related to the concentrations of plasma lipids in spite of the fact that it was found to be elevated in hyperlipoproteinaemic subjects. The results though preliminary suggest that in diabetic patients the concentration of soluble adhesion molecules and especially of E-selectin may be related to metabolic control.
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PMID:Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control. 881 15

Diabetic retinal neovascularisation is considered to be a consequence of retinal ischaemia caused by capillary occlusion. Capillary occlusion is the result of microvascular thrombi in which erythrocytes, platelets and leucocytes each may play a role. We investigated the role of leucocytes in this process and the subsequent angiogenic response. We studied the serum levels of the soluble leucocyte adhesion molecules soluble E-Selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in the serum of 93 patients with insulin-dependent diabetes (IDDM) and varying degrees of retinopathy and 47 healthy age and sex matched control subjects. We also measured the ability of serum to stimulate retinal capillary endothelial cell migration using an assay of angiogenesis in vitro. Soluble E-Selectin and sVCAM-1 levels were raised in all patients with IDDM (p < 0.001; p < 0.001) particularly those with retinopathy (p < 0.001; p < 0.001). Soluble E-Selectin levels were highest in the patients with severe non-proliferative diabetic retinopathy (p < 0.001) and sVCAM-1 levels were highest in patients with proliferative diabetic retinopathy (p < 0.01). In contrast soluble ICAM-1 levels were the same in patients and control subjects (p > 0.05). Soluble E-Selectin levels in diabetic patients were correlated with the level of glycated haemoglobin (p < 0.05). Retinal endothelial cell migration-inducing (ECMI) activity was increased in patients with IDDM (p < 0.01) in particular in those with retinopathy (p < 0.01). Furthermore, in vitro ECMI activity could be blocked by antibodies to sVCAM-1 and sE-Selectin. These data point to a functional role for leucocyte adhesion in the microvasculopathy of diabetic retinopathy and may have implications for the induction of retinal angiogenesis.
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PMID:Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration. 934 97

AECA were detected in 25 of 71 patients with type 1 diabetes mellitus and in two of 33 healthy subjects. Patients with diabetes of < 1 year duration and those with long-standing disease had the highest levels of these antibodies. Inhibition studies suggest that at least part of the AECA reactivity is due to cross-reactive anti-ssDNA antibodies. AECA-positive sera were able to increase intercellular adhesion molecule-1 (ICAM-1) and E-selectin on human umbilical vein endothelial cells (HUVEC). Increased binding of polymorphonuclear (PMN) cells was also found to accompany raised E-selectin expression. Soluble ICAM-1 and E-selectin were also found to be increased in the sera of AECA-positive patients. An effect of AECA on endothelial cell function is suggested in diabetes mellitus.
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PMID:IgG anti-endothelial cell antibodies (AECA) in type I diabetes mellitus; induction of adhesion molecule expression in cultured endothelial cells. 952 88

Recent developments in cell biology have identified new areas of direct relevance to the pathogenesis of Type 1 (insulin-dependent) diabetes mellitus and its complications. Endothelial damage is well recognized in diabetes--endothelial cell markers von Willebrand factor, soluble E-selectin, and soluble thrombomodulin are providing further evidence of the relationship between activation and damage to the vasculature and clinical disease in this condition. Cell surface bound adhesion molecules may also have a role in the development of atherosclerosis in patients with diabetes but the importance of the soluble forms of these molecules, such as intercellular adhesion molecule-1, is unclear. Evidence of platelet dysfunction has long been acknowledged in diabetes and new data are discussed. It is likely that a greater appreciation of the intimate interactions between endothelial integrity, adhesion molecules and platelets in Type 1 diabetes mellitus will provide a greater understanding of the risk of cardiovascular disease and stroke in patients with this disorder.
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PMID:Endothelial integrity, soluble adhesion molecules and platelet markers in type 1 diabetes mellitus. 1022 99

Pancreases of untreated and nicotinamide (NIC)-treated pre-diabetic (10-week-old) and overtly diabetic (25-week-old) female NOD (non-obese diabetic) mice and of NON (non-obese non-diabetic) control mice were studied, with the following results. (1) Islets and ducts of overtly diabetic untreated NOD mice (25-week-old) were found to express low levels of MHC class I and II molecules, like NON controls, and high levels of adhesive molecules. (2) NIC was able to slightly affect glycaemia and insulitis, slowing down diabetes progression. Moreover it significantly decreased MHC class II expression (but not class I) in vivo by week 10, and significantly enhanced intercellular adhesion molecule-1 (ICAM-1) expression, mainly by week 25, within the pancreas, where 5-bromo-2'-deoxyuridine positive nuclei and insulin positive cells were present, demonstrating that a stimulation of endocrine cell proliferation occurs. (3) In addition, NIC partly counteracted the fall of superoxide dismutase levels, observed in untreated diabetic NOD animals. (4) In vitro studies demonstrated that NIC: (i) was able to significantly reduce nitrite accumulation and to increase NAD+NADH content significantly, and (ii) was able to increase the levels of interleukin-4, a T helper 2 lymphocyte (Th2) protective cytokine, and of interferon-alpha (IFN-alpha), which is known to be able to induce MHC class I and ICAM-1 but not MHC class II expression, as well as IFN-gamma, which is also known to be able to induce MHC class I and ICAM-1 expression. The latter, although known to be a proinflammatory Th1 cytokine, has also recently been found to exert an anti-diabetogenic role. This study therefore clearly shows that adhesive mechanisms are ongoing during the later periods of diabetes in pancreatic ducts of NOD mice, and suggests they may be involved in a persistence of the immune mechanisms of recognition, adhesion and cytolysis and/or endocrine regeneration or differentiation processes, as both NIC-increased ICAM-1 expression and 5-bromo-2'-deoxyuridine positivity imply. The effects of NIC on MHC class II (i.e. a reduction) but not class I, and, mainly, on ICAM-1 expression (i.e. an increase), together with the increase in Th2 protective cytokine levels are very interesting, and could help to explain its mechanism of action and the reasons for alternate success or failure in protecting against type 1 diabetes development.
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PMID:Nicotinamide decreases MHC class II but not MHC class I expression and increases intercellular adhesion molecule-1 structures in non-obese diabetic mouse pancreas. 1007 85

We investigated the intercellular adhesion molecule-1 (ICAM-1) gene polymorphism in 90 patients with young-onset type 1 diabetes, 74 with adult-onset type 1 diabetes, and 171 control subjects. The distribution of C-T genotypes and allele frequencies in exon 6 of the ICAM-1 gene was significantly different between adult-onset type 1 diabetes patients and controls (chi(2) = 9.76, p = 0.0076), and between patients with adult-onset and young-onset type 1 diabetes (chi(2) = 11.28, p = 0.0036). In contrast, we failed to detect any association between patients with young-onset type 1 diabetes and controls. Our data suggest that ICAM-1 exon 6 gene polymorphism affects the age-at-onset of type 1 diabetes and that different pathogenetic mechanisms may exist between young-onset and adult-onset type 1 diabetes.
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PMID:Association between type 1 diabetes age-at-onset and intercellular adhesion molecule-1 (ICAM-1) gene polymorphism. 1077 53

The intercellular adhesion molecule-1 (ICAM-1) has an important role in the process of lymphocyte migration and activation, and is supposed to be involved in the pathogenesis of type 1 diabetes. We studied A/G (K469E) polymorphism of the ICAM-1 gene in 218 type 1 diabetes patients and 212 controls from Finland and found no association. We then studied transmission of the ICAM-1 alleles in 102 Finnish families using a transmission disequilibrium test (TDT). Alleles A and G were transmitted to the affected offspring in 50% each. Stratification by the HLA-DQB1-DQA1 genotypes, sex and age at onset did not reveal association. Our data demonstrate that in the Finnish population K469E polymorphism of the ICAM-1 gene is not associated with type 1 diabetes.
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PMID:Intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism: no association with type 1 diabetes among Finns. 1090 13

Type 1 (insulin-dependent) diabetes is a complex trait. The region harboring the ICAM1 gene on 19p13 links to type 1 diabetes, and a growing body of evidence indicates that intercellular adhesion molecule-1 (ICAM-1) could play a role in type 1 diabetes development. Recently, association studies of an ICAM-1 K469E polymorphism in type 1 diabetes populations have reported conflicting results. Hence, we performed a transmission disequilibrium test analysis of the ICAM-1 K469E variations in 253 Danish type 1 diabetes families. Linkage and association was not found between the ICAM-1 K469E variation and type 1 diabetes in Danish patients (P(tdt)> or =0.48), and our data did not indicate an interaction between ICAM1 and IDDM1 in predisposition to type 1 diabetes in Danes (P=0.78). We did not observe significant association with late-onset type 1 diabetes (P(tdt)> or =0.12) or differences in transmission patterns between groups of affected offspring stratified for age at onset (P> or =0.19), as suggested in Japanese patients. Combined analysis of the present and previously reported transmission data comprising 728 affected offspring of Romanian, Finnish, and Danish ancestry suggested association between the ICAM-1 E469 allele and type 1 diabetes (P(tdt)=0.013), but association was not found in the combined Scandinavian material. In conclusion, we found no association of the ICAM-1 K469E polymorphism with type 1 diabetes or its subsets stratified for age at onset and HLA risk in Danish patients. Analysis of ICAM-1 K469E transmissions reported in three populations suggested association to type 1 diabetes, but also demonstrated heterogeneity between populations.
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PMID:The intercellular adhesion molecule-1 K469E polymorphism in type 1 diabetes. 1113 45


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