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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Encephalomyocarditis (EMC) virus induction of diabetes mellitus in mice has proven to be an excellent experimental model for the pathogenesis of viral disease. In SJL and DBA/2 mice, diabetes results exclusively from the infection and damage of beta cells by the virus. In addition, in BALB/cBy mice subclinical beta cell damage caused by the virus is followed by autoimmune beta cell destruction, which results in hyperglycemia. Studies of two closely related plaque variants (EMC-D and EMC-B) selected from the M strain of EMC virus revealed differences in the interferon response associated with viral infection. The EMC-D variant causes diabetes in infected SJL mice by direct beta cell destruction. Infection with EMC-B does not cause diabetes and interferes with the production of diabetes by EMC-D due to the greater ability of EMC-B than of EMC-D to induce interferon in mice. Circulating interferon has a greater effect on inhibition of viral replication because local interferon production is amplified in interferon-primed cells infected with EMC-B. These properties are determined by the interferon-inducing particle (Ifp+) phenotype of EMC-B and the Ifp- phenotype of EMC-D.
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PMID:Encephalomyocarditis virus-induced diabetes mellitus in mice: model of viral pathogenesis. 282 21

A study of Class I and II major histocompatibility complex gene product expression by a rat insulinoma cell line (RINm5F) was performed using monoclonal antibodies and immunoperoxidase techniques. RINm5F cells were incubated with different concentrations of gamma interferon. RINm5F cells exhibit low levels of Class I molecules and are normally devoid of Class II gene products. Upon exposure to gamma interferon, RINm5F cells showed a dramatic increase in Class I expression. This expression was homogenous and could be detected on all cells after 18 h of incubation with as little as 1 unit/ml of interferon. In contrast, de novo Class II expression was not homogeneous and required 36 h of incubation with 10 units/ml of interferon. The number of RINm5F cells expressing Class II antigens was dose- and time-dependent. Interferon treatment did not affect the morphology of RINm5F cells as determined by ultrastructural analysis. Withdrawal of interferon from the culture medium for as long as 78 h diminished but did not abolish the expression of Class I and Class II molecules already induced. The ability of interferon to enhance expression of Class I gene products and induce de novo expression of Class II molecules on B-cell-derived RINm5F cells supports the hypothesis that aberrant expression of major histocompatibility complex gene products on pancreatic B cells may be an important factor in triggering the immune response in Type 1 (insulin dependent) diabetes mellitus.
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PMID:Class I and II major histocompatibility complex gene product expression by a rat insulinoma cell line in vitro following exposure to gamma interferon. 285 88

The induction of insulin-dependent diabetes in outbred male and female mice was examined using a combination of the usually nondiabetogenic B-variant of encephalomyocarditis (EMC-B) virus and single low doses of streptozocin (STZ). Neither EMC-B virus nor low doses of STZ were overtly diabetogenic when administered alone; however, when these two insults occurred 1 day apart, diabetes resulted in male but not in female mice. The induction of diabetes was dependent on the time interval between these two insults, since EMC-B virus and STZ given 4 days apart did not induce diabetes. Unexpectedly, when the order of these two insults was reversed, diabetes occurred. The absence of diabetes when EMC-B virus was given before STZ suggested the possibility that virus-induced interferon blocked the cytotoxic effects of STZ. This suggestion was supported by the observation that an antiserum against beta interferon abrogated the virus-mediated protection against STZ-mediated cytotoxicity. Also, Poly I:C administered before a single diabetogenic dose of STZ delayed the onset of severe hyperglycemia.
Diabetes 1985 Dec
PMID:A murine model of insulin-dependent diabetes mellitus resulting from the cumulative effects of the nondiabetogenic strain of encephalomyocarditis virus and a single low dose of streptozocin. 299 12

The D variant of encephalomyocarditis virus (EMCV-D) induces a diabetes mellitus-like disease in male SJL/J mice. Other inbred strains, while resistant to the diabetogenic effect, exhibit strikingly different responses to this virus. In these studies, infection of diabetes resistant C3H mice with the D variant produces massive acute pancreatitis with little apparent direct islet cell involvement. This exocrine tropism is not altered when C3H mice with an inherent macrophage defect are infected, and appears to be a gender-specific phenomenon, with female C3H mice resistant to this exocrine involvement. Long-term infection of both male and female C3H mice does not change their response to the virus. Castration of male C3H mice, using a protocol that has been reported to block the diabetogenic effect of this virus, does not alter the development of this acinar lesion. The B variant of EMCV does not induce acinar destruction, nor is it diabetogenic. However, preinfection with the B variant 3 days prior to infection with the D variant does protect against the development of the exocrine lesion. Coinfection with equal doses of the two variants also protects against this lesion, as does coinfection with a lower dose of B variant. Therefore, the host response that is generated against the B variant appears to be responsible for this protection from D variant exocrine destruction. Due to the short time frame, it is unlikely that this protection is the result of an antibody response. Rather, this data is more consistent with an interferon response generated against the B variant that would inhibit replication of the D variant.
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PMID:Altered pathogenesis in encephalomyocarditis virus (D variant)-infected diabetes-susceptible and resistant strains of mice. 301 7

Islets from male B10.BR mice (H-2k) were isolated by the collagenase technique, handpicked with a Pasteur pipette, and incubated (either intact or after dispersion with Dispase) for 0, 3, 5, 7, 10, or 14 days in tissue culture medium supplemented with either lymphokine supernatants or recombinant murine interferon-gamma. Islets and single cells were examined for IAk molecules by use of indirect immunofluorescence. Ia-positive islet cells were identified on the surface of islets incubated with 5-10% lymphokine for greater than 4 days or with 10, 100, or 1000 ng/ml interferon for greater than 6 days. Islets incubated in unsupplemented medium were Ia negative. Incubation with 5% lymphokine induced Ia expression on 10-40% dispersed islet cells cultured for greater than 9 days. Dual immunofluorescent staining for Ia and insulin revealed that Ia-positive cells included both beta- and non-beta-cells.
Diabetes 1986 Oct
PMID:Interferon-mediated induction of Ia antigen expression on isolated murine whole islets and dispersed islet cells. 309

Inappropriate expression of HLA Class II (D/DR) molecules has been detected in the target cells of most autoimmune diseases including Type I (insulin-dependent) diabetes. The possibility that this phenomenon is due to the action of lymphocytes or some of their products has been investigated by analysing in vitro the modulation of HLA products in Beta cells. Monolayer cultures from 25 human pancreatic glands were supplemented with alpha-interferon (IFN), beta-IFN or gamma-IFN, interleukin 2 (IL-2) and supernatants from activated lymphocytes. In addition, lectins and a variety of other hormones, biological products and chemicals were tested. Major histocompatibility complex (MHC) expression was assessed by double immunofluorescence technique using monoclonal antibodies to non-polymorphic determinants of Class I and Class II molecules and the pancreatic cells were identified by antibodies to islet hormones and other cytoplasmic antigens. gamma-IFN and lectins produced a parallel enhancement of HLA-A,B,C expression in islet, exocrine/ductal cells and fibroblasts. HLA-D/DR was inducible in all pancreatic cell types, except endocrine islet cells which did not produce Class II molecules in response to any of the stimuli including supernatants from activated lymphocytes. Exocrine/ductal cells from glands of patients with chronic pancreatitis spontaneously expressed Class II products, but islet cells were devoid of any detectable D/DR. These data are consistent with recent observations which have indicated that in the 'diabetic' pancreas inappropriate Class II expression in the Beta cells occurs independently of the presence of lymphocytes infiltrating the islets, and make it necessary to postulate that other factors are responsible for the Class II induction in Beta cells in human Type I diabetes.
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PMID:Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas. 309 71

Previous studies have shown several immunoregulatory abnormalities in insulin-dependent diabetes mellitus (IDDM). In this report we compared peripheral blood mononuclear cells (PBMC) from patients with IDDM complicated by end-stage renal disease (ESRD) to those from normal subjects and from patients with ESRD of different etiologies for their: natural killer (NK) and antibody-dependent cell-mediated cytotoxic (ADCC) activities; modulation of NK and ADCC activities by biological response modifiers (BRM) including purified human lymphoblastoid interferon, human recombinant alpha-2 interferon, human gamma interferon and human recombinant interleukin 2; proliferative response of T and B lymphocytes to concanavalin A (Con A), phytohemagglutinin and pokeweed mitogen, and ability to produce T-cell growth factor (interleukin 2; IL-2). PBMC of diabetic patients demonstrated significantly lower NK activity than normal and ESRD subjects. Upon treatment with BRM, NK activity was augmented and achieved normal levels. ADCC activity was not different from that of normal controls and exhibited similar increases when stimulated by BRM. The proliferative responses to Con A, phytohemagglutinin and pokeweed mitogen as well as IL-2 production in response to Con A stimulation were significantly lower in the IDDM group. Our results indicated that NK cells from patients with IDDM can respond to IL-2 with enhanced cytotoxicity, and, because activation of resting T cells by mitogenic stimuli depends on the production of IL-2 as well as the appearance of a receptor for IL-2, our finding of low levels of in vitro IL-2 production by PBMC from patients with IDDM may explain the depressed NK activity and the observed poor response to T-cell mitogens.
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PMID:Cell-mediated immunity and biological response modifiers in insulin-dependent diabetes mellitus complicated by end-stage renal disease. 311 74

Pancreatic endocrine cells normally express only Class I gene products of the major histocompatibility complex (MHC). Recently it has been shown that in both patients with recent onset type I diabetes and acutely diabetic BB rats, residual islet beta cells express Class II MHC antigens. In an attempt to define a potential inducer of this aberrant Class II antigen expression, we have investigated the effect of in vitro incubation of rat isolated pancreatic islets with the lymphokine gamma interferon (IFN-gamma) on MHC antigen expression. Our results demonstrate that in vitro exposure to IFN-gamma induces novel expression of Class II antigens on the surface of rat islet endocrine cells and increases the level of pre-existing Class I antigen expression.
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PMID:Gamma interferon induces novel expression of Ia antigens by rat pancreatic islet endocrine cells. 311 39

BB rats are prone to develop an autoimmune form of insulin-dependent diabetes mellitus (IDDM) and thyroiditis. Development of autoimmunity is thymus dependent. Previous studies have shown that BB rats lack a population of T cells bearing the RT6 antigen and have very low numbers of suppressor/cytotoxic T cells. In this study, we confirm that BB rats have decreased numbers of phenotypic T suppressor/cytotoxic (Ts/c) cells (OX19+, OX8+ cells) in their lymphoid organs. Moreover, we find that the phenotypic Ts/c cells of BB rats lack apparent cytotoxic activity. These T cells fail to kill allogeneic target cells in a cell-mediated lympholysis assay and fail to generate lectin-dependent cytotoxicity. The addition of interleukin 2, gamma-interferon, and other lymphokines to cultures of BB T cells does not induce functional cytotoxic T lymphocytes. We find that the activated T cells of newly diabetic rats are incapable of killing major-histocompatibility-complex-matched islet cells, despite the ability of these cells to cause IDDM in passive transfer experiments. We conclude that autoimmune disease occurs in BB rats in the absence of functional cytotoxic T cells.
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PMID:Autoimmunity-prone BB rats lack functional cytotoxic T cells. 313 Oct 22

Autopsy pancreases were studied from 14 patients who had idiopathic Addison's disease. One patient had been diabetic for 12 years and three patients were found to be diabetic during their terminal admission. While there was no evidence of diabetes or destruction of insulin-secreting beta cells in the remaining 10 patients, islets in one pancreas exhibited many of the histological and immunohistochemical features seen in the patients with recent onset diabetes. These included the presence of alpha-interferon in endocrine cells, hyper-expression of class I major histocompatibility complex molecules by endocrine cells in islets where alpha-interferon was also present, aberrant expression of class II major histocompatibility complex molecules by endocrine cells and the presence of insulitis. Since the combination of these changes has only been described in type 1 diabetes it is thought that the appearances seen in this pancreas were those of prediabetes.
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PMID:The pancreas in idiopathic Addison's disease--a search for a prediabetic pancreas. 339 44


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