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)

Islet-specific autoimmune reactivity (humoral and cell-mediated) is the basis for the insulitis process of type I diabetes mellitus. In this report a delayed-type hypersensitivity (DTH) skin test was used to monitor the presence of an islet-specific cell-mediated autoimmune component in BB/O rats. The BB/O rat is a strain characterized by the spontaneous development of type I diabetes. Intact RINm5F cells as well as a RINm5F cell membrane preparation were used as DTH skin test antigens. Rats of different ages and disease stages were tested in the ear with the insulinoma cell line and its cell membrane preparation. As control antigens, the fibroblast cell line 3Y1 and a cell membrane preparation made thereof were used. The DTH reaction system showed a positive cell-mediated reactivity in BB/O rats for membrane-bound RINm5F cell antigens, and not for the control fibroblast 3Y1 cell membrane determinants. The true DTH character of the skin test was established by the time-course of the reaction (maximum at 24 h), the histopathology (infiltration by dendritic cells, lymphocytes and macrophages), and the possibility to transfer the reaction with spleen cells and lymph node cells. The DTH test towards RINm5F cells showed the highest prevalence of positivity (100%) in BB/O rats around the onset of diabetes (3 weeks before to 3 weeks after the onset of glucosuria). The prevalence of DTH positivity was 56% in the period of more than 3 weeks before the onset of glucosuria. In BB/O rats with a duration of glucosuria of more than 3 weeks, the prevalence of positivity was around 60-70%.
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PMID:A delayed-type hypersensitivity skin-test system using the insulinoma cell line RINm5F to monitor beta cell-specific cellular autoimmune reactivity in the spontaneously diabetic BB/O rat. 226 92

The incidence of fasting HLP in 326 diabetics was 68.4 percent. The common types of HLP were type IV, IIb, IIa and III respectively. There was one case of type V. HDLC was decreased in all three groups of diabetics together with elevated ratio of TC to HDLC comparing with the controls of similar age and sex VLDL and TG were significantly elevated in NIDDM aged 60 and over comparing with IDDM but not significantly different from NIDDM aged below 60. The early detection and treatment of HLP along with optimum control of blood glucose are of utmost importance to prevent further complications caused by atherosclerosis.
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PMID:Lipid disorders in Thai diabetics. 668 May 38

The diabetic syndrome in the DP-BB rat results from progressive beta-cell destruction by autoimmune responses. However, the initial events causing the autoimmune destruction of beta cells remain largely unknown. Our recent experimental results suggest that the delayed expression of a beta-cell-specific autoantigen may result in the initiation of beta-cell-specific autoimmunity. The present investigation was initiated to identify such an autoantigen. Islets were isolated from DP-BB rats of several different ages, and protein extracts from the membrane fraction of the islet preparations were immunoprecipitated with sera from diabetic DP-BB rats. We have found that a membrane-bound islet cell-specific 38 kDa autoantigen is not expressed early in the life of DP-BB rats, but is delayed-expressed by approximately 30 days of age, the time at which immunological effectors begin to recognize beta cells. In contrast, a 64 kDa islet cell protein is expressed from birth in DP-BB rats. On the basis of these observations, we suggest that delayed expression of a gene encoding for the membrane-bound islet cell-specific 38 kDa autoantigen may result in a breakdown of self-tolerance, leading to beta-cell-specific autoimmune IDDM in the BB rat.
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PMID:Studies on autoimmunity for initiation of beta-cell destruction. X. Delayed expression of a membrane-bound islet cell-specific 38 kDa autoantigen that precedes insulitis and diabetes in the diabetes-prone BB rat. 805 82

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T (IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the beta-chain (V beta 7) in these IIT cells in association with unselected V alpha-chain segments; extensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.
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PMID:Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology. 809 Jan 94

SEZ-12 is one of the seizure-related cDNAs which was isolated by differential hybridization from primary cultured neurons from the mouse cerebral cortex with or without pentylenetetrazol (PTZ). SEZ-12 expression is transiently down-regulated in the mouse brain by injection of PTZ. To characterize SEZ-12, isolation of full-length cDNA and nucleotide sequence analysis were performed. The deduced amino acid sequence of SEZ-12 revealed that it encodes membrane-bound C-type lectin and has a significant homology to that of human cDNA, DGCR2 and IDD, which were cloned from a balanced translocation breakpoint associated with the DiGeorge syndrome. The isolated cDNA was about 4 kb in length and the message was expressed ubiquitously in various organs with low-abundance. Previously, we also cloned a transmembrane protein which is probably involved in cell-cell interaction by the differential hybridization technique. These findings suggest that transmembrane signaling in neuronal cells may have an important role in PTZ-induced seizure.
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PMID:Cloning of SEZ-12 encoding seizure-related and membrane-bound adhesion protein. 863 60

Na+/K(+)- and Ca(2+)-ATPase are the major ATP-dependent membrane-bound enzymes that regulate the cation transmembrane gradient which is altered both in red blood cell (RBC) senescence and in RBCs of diabetic patients. In an attempt to clarify the possible connection between diabetes mellitus and ageing, we investigated the relationship between RBC ATP content, Na+/K(+)-ATPase, Ca(2+)-ATPase activities and ageing in healthy, insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) subjects. A significant correlation was found (r = -0.82; P < 0.001) between RBC ATP content and subject's age only in the control group. A significant reduction in Na+/K(+)-ATPase activity was observed in the older group (C2) of control subjects, in comparison with the younger (C1) one. In both IDDM and NIDDM subjects, the enzymatic activity was significantly decreased when compared with health subjects of similar age (P < 0.001). A significant negative correlation was found between age and enzymatic activity in healthy subjects (r = -0.60; P < 0.001). No difference was observed in the RBC membrane Ca(2+)-ATPase activity between younger (C1) and older (C2) healthy subjects. Ca(2+)-ATPase activity was significantly increased both in IDDM patients compared with C1 (P < 0.001) and in NIDDM patients compared with C2 (P < 0.001). The present data indicate that ageing causes a reduction in the erythrocyte ATP content in both healthy and diabetic subjects. In diabetic patients Na+/K(+)-ATPase activity decreases independently of age.
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PMID:Diabetes mellitus and subjects' ageing: a study on the ATP content and ATP-related enzyme activities in human erythrocytes. 913 82

Adhesion molecules play an important role during leukocyte emgration from blood vessels. Furthermore, adhesion molecules are involved in the regulation of the immune system. In addition to membrane-bound adhesion molecules soluble forms have been detected in human serum. During the last few years we have analysed the role of adhesion molecules during the pathogenesis of type 1 diabetes. This review describes the results of studies on membrane-bound and soluble adhesion molecules in humans and the model of the NOD mouse. Based on these results different adhesion molecule-specific immunotherapies are presented for the prevention of type 1 diabetes and its preclinical stages.
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PMID:Soluble adhesion molecules in type 1 diabetes mellitus. 949 3

Treatment with high doses of nicotinamide (niacinamide, vitamin B3) prevents or delays insulin-deficient diabetes in several animal models of type 1 diabetes and protects islet cells against cytotoxic actions in vitro. In recent-onset type 1 diabetes, nicotinamide administration improves beta-cell function, without significantly decreased insulin requirements. This review discusses the possible mechanism of action of nicotinamide in vivo. It is proposed that the key target of nicotinamide is the poly(ADP-ribose)polymerase (PARP), and to a lesser extent (mono)ADP-ribosyl transferases (ADPRTs). Suppression of PARP activity by nicotinamide not only decreases consumption of NAD+, the substrate of PARP, but also has major regulatory effects on gene expression, as shown for the major histocompatibility complex class II gene. In addition, PARP activity controls early steps of apoptosis. The possible suppression of ADPRTs by nicotinamide would also affect CD38, a membrane-bound external ADP-ribosyl transferase with potent immunoregulatory properties. Taken together, it is proposed that high doses of nicotinamide primarily affect ADP-ribosylation reactions in beta-cells as well as in immune cells and the endothelium. As a consequence, cell death pathways and gene expression patterns are modified, leading to improved beta-cell survival and an altered immunoregulatory balance.
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PMID:Nicotinamide in type 1 diabetes. Mechanism of action revisited. 1009 94

Various therapeutic strategies have been developed to tolerize autoreactive T cells and prevent autoimmune pathology in type 1 diabetes. 4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor primarily expressed on activated T cells. The administration of an agonistic anti-4-1BB antibody (2A) dramatically reduced the incidence and severity of experimental autoimmune encephalomyelitis (EAE). Treatment with the same antibody in Fas-deficient MRL/lpr mice blocked lymphadenopathy and lupus-like autoimmune processes. Paradoxically, transgenic non-obese diabetic (NOD) mice overexpressing membrane-bound agonistic single-chain anti-4-1BB Fv in pancreatic beta cells developed more severe diabetes than their non-transgenic littermates, with earlier onset, faster diabetic processes, and higher mortality. Forty percent of transgenic mice developed diabetes by 4 weeks of age, compared with their control littermates, which first exhibited diabetes at 14 weeks. The frequency of diabetes in female transgenics reached 70% by 8 weeks of age. Most female transgenic mice died around 12 weeks. Consistent with this, transgenic mice developed earlier and more severe insulitis and showed stronger GAD-specific T-cell responses, compared with age-matched control littermates. Our results indicate an adverse effect of transgenic anti-4-1BB scFv in NOD mice and suggest a potential risk of this anti-4-1BB-based immunotherapy for autoimmune diseases.
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PMID:Anti-4-1BB-based immunotherapy for autoimmune diabetes: lessons from a transgenic non-obese diabetic (NOD) model. 1459 49

One mechanism whereby B cells contribute to type 1 diabetes in nonobese diabetic (NOD) mice is as a subset of APCs that preferentially presents MHC class II-bound pancreatic beta cell Ags to autoreactive CD4 T cells. This results from their ability to use cell surface Ig to specifically capture beta cell Ags. Hence, we postulated a diabetogenic role for defects in the tolerance mechanisms normally blocking the maturation and/or activation of B cells expressing autoreactive Ig receptors. We compared B cell tolerance mechanisms in NOD mice with nonautoimmune strains by using the IgHEL and Ig3-83 transgenic systems, in which the majority of B cells recognize one defined Ag. NOD- and nonautoimmune-prone mice did not differ in ability to delete or receptor edit B cells recognizing membrane-bound self Ags. However, in contrast to the nonautoimmune-prone background, B cells recognizing soluble self Ags in NOD mice did not undergo partial deletion and were also not efficiently anergized. The defective induction of B cell tolerance to soluble autoantigens is most likely responsible for the generation of diabetogenic APC in NOD mice.
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PMID:B cell selection defects underlie the development of diabetogenic APCs in nonobese diabetic mice. 1506 92


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