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

A possible contribution of the immune system to the pathogenesis of virus-induced diabetes mellitus was investigated using the D-variant of encephalomyocarditis (EMC-D) virus. Studies on the F1 and backcross progeny of susceptible and resistant strains of mice gave no suggestion of a linkage between susceptibility and the major histocompatibility locus. Immuno-suppression by antilymphocyte serum did not prevent the induction of EMC-D-induced diabetes. Athymic nude mice infected with EMC-D virus showed a nearly identical diabetogenic response as compared with heterozygous littermates. Passive transfer of lymphocytes from mice made diabetic with EMC-D virus into normal mice failed to produce diabetes. From these and other studies, we conclude that the development of EMC-D-induced diabetes is due to the direct destruction of beta-cells by the virus and that the contribution of the immune response to the pathogenesis of this disease is, at the most, minor.
Diabetes 1985 Sep
PMID:Virus-induced diabetes mellitus. No evidence for immune mechanisms in the destruction of beta-cells by the D-variant of encephalomyocarditis virus. 299 85

DBA/2 and Balb/cBY mice were infected with approximately 30 plaque-forming units of the M-variant of encephalomyocarditis (EMC-M) virus. Seven days after inoculation the majority of the animals of both strains were hyperglycemic. A significant correlation between increased concentrations of virus in the pancreas and hyperglycemia was found among individual DBA/2 animals, but not among Balb/cBY mice. T-lymphocyte depletion of DBA/2 mice before infection failed to alter the incidence or severity of hyperglycemia in comparison to intact animals. Conversely, hyperglycemia in T-lymphocyte-depleted Balb/cBY mice was reduced substantially in comparison to infected immunocompetent animals. There appears to be at least two genetically influenced pathogenic mechanisms of diabetes in EMC-M virus-infected mice. In some strains of animals, hyperglycemia results exclusively from viral infection and the consequent injury to the beta cells, whereas in other animals, viral damage to the islets is compounded by immunologic events.
Diabetes 1985 Nov
PMID:Genetic influences on the immunologic pathogenesis of encephalomyocarditis (EMC) virus-induced diabetes mellitus. 299 82

Adult, male ICR Swiss mice are susceptible to the diabetogenic effects of the D-variant of encephalomyocarditis virus (EMC-D) in contrast to adult C3H/HeJ male mice, which are relatively resistant. To date, experimental evidence suggests that the immune system plays a role in the pathogenesis of this infection. We have investigated the potential involvement of the immune system in the pathogenesis of EMC-D-induced diabetes using cyclosporin-A (CyA), a potent immunosuppressive drug. The data show that treatment with CyA results in increased severity and incidence of diabetes in susceptible ICR Swiss mice and induction of diabetes in resistant C3H/HeJ mice. It is concluded that immune mediation probably is not involved in the early pathogenesis of EMC-D-induced diabetes in mice.
Diabetes 1985 Dec
PMID:Virus-induced murine diabetes. Enhancement by immunosuppression. 299 10

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

Adult male ICR Swiss mice develop insulin-dependent diabetes when infected with the D variant of encephalomyocarditis virus (EMC-D). In contrast, adult C57Bl/6 males are relatively resistant to the diabetogenic effects of this virus. We have been studying the role of interferon (IFN) in the pathogenesis of infection by EMC-D and development of virus-induced murine diabetes mellitus. The data show that when IFN beta or IFN gamma were administered four days after virus infection, the frequency and severity of diabetes were exacerbated in ICR Swiss mice, and the diabetic state was induced in the resistant C57Bl/6 strain. In addition, animals treated with either of the IFNs or the IFN-inducer poly I:C, developed symptoms of severe encephalomyocarditis. Analysis of ICR Swiss mouse tissues revealed that IFN-treatment resulted in virus replication in the heart and brain and the reappearance of the virus in the pancreas. It is concluded that under certain conditions, the diabetic state is exacerbated and the normal course of (EMC-D)-infection in mice is altered by IFN.
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PMID:Exacerbation of the pathogenesis of the diabetogenic variant of encephalomyocarditis virus in mice by interferon. 388 8

The pathogenesis of EMC virus induced diabetes has generally been thought to be caused by direct cytopathic effect of the virus on beta cells with susceptibility or resistance dictated primarily by the density of viral receptors on the beta cells of different individuals. The histological finding of insulitis, our demonstration of a protective effect of immunosuppression with ALS or anti-theta antibody and silica supports host immune factors as important determinants of susceptibility. A critical role of the immune system might be mediated by autoimmune destruction of EMC-virus infected beta cells. In susceptible strain mice treated with low dose cyclophosphamide to deplete suppressor cells, which may halt the autoimmune process and allow recovery, a prolonged period of hyperglycemia was demonstrated as compared to controls. Bone marrow exchanged between susceptible and resistant strains was also found to alter susceptibility. "B mice", deficient in T lymphocytes, when infected with EMC virus had a decreased incidence of diabetes. Susceptibility to EMC diabetes may be dictated by the autoaggressive response of host immune system to beta cells altered by EMC virus infection.
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PMID:The importance of immunologic factors in the pathogenesis of encephalomyocarditis virus induced diabetes in mice. 609 11

EMC virus-induced diabetes in mice may be a model of human type I diabetes. It is postulated that auto-immune reaction plays a role in beta cell destruction after viral aggression. The use of anti-viral (interferon) or immunosuppressive drugs (Cyclosporin A) could contribute to an understanding of the pathogenesis of diabetes in this model. Early or late administration of cyclosporin A increased mortality and frequency of diabetes in female mice and did not influence these parameters in males despite a reduction of pancreatic inflammatory lesions. Interferon administered at the time of virus inoculation diminished mortality in both sexes and frequency of diabetes in males. These results are against an autoimmune pathogenesis for diabetes in this model and suggest that the virus plays the major role in beta cell damage.
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PMID:Assessment of viral and immune factors in EMC virus-induced diabetes: effects of cyclosporin A and interferon. 618 14

The diabetogenic variant of encephalomyocarditis virus (EMC-D) induces a diabetes-like syndrome in certain strains of mice. A study was done to determine if virus-induced diabetes could be prevented by interferon (IFN). It was found that the production of diabetes by EMC-D was blocked by either IFN beta or a variety of IFN-inducers in SWR/J, but not ICR Swiss mice. The replication of EMC-D in cell culture was inhibited by IFN beta. It is concluded that the response of pancreatic beta cells to the protective effect of IFN, is probably under genetic control.
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PMID:Inhibition of virus-induced diabetes mellitus by interferon is influenced by the host strain. 630 72

Much clinical and experimental data is in support of a significant role played by viruses in the etiology of diabetes mellitus. This hypothesis is borne out by the association of diabetes mellitus with Coxsackie B, mumps, rubella and herpes simplex virus infections, the presence of high persistent titers of neutralizing antibodies in diabetic patients, the in vitro permissiveness of human beta cells to viruses, and the recovery of viruses from the pancreas of diabetic patients. Viral multiplication is facilitated in HLA B8, B15, B18, Dw3 and Dw4 carriers. Experimental inoculation of EMC and Coxsackie B viruses to mice shows that beta cell involvement is dependent upon viral strains, viral membrane receptors, interferon production, immunological response and less essential factors such as age and sex. The virus is responsible for a specific immunological response and produces autoimmunological phenomena. These result in a decrease in the number and activity of insulin-producing cells through cytotoxic mechanisms. Pathological findings corroborate these physiopathological hypotheses.
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PMID:[Viruses and juvenile diabetes mellitus]. 632 9

The best experimental evidence indicating that viruses have an etiological role in the pathogenesis of diabetes comes from studies of mice infected with EMC virus. For this study we generated mutant viruses from stocks of diabetogenic EMC-D and nondiabetogenic EMC-B viruses by serial passages of the viruses in L-cell cultures at high MOI. The genomic sequence information and the biological activities of three different plaque-purified diabetogenic variants of EMC virus (EMC-D, EMC-D1/6A, EMC-D2/4) and six different plaque-purified nondiabetogenic variants (EMC-B, EMC-BS, EMC-B1/G, EMC-DV1, EMC-D4/1B, EMC-D3/1) revealed that only one amino acid, Ala (776th amino acid on the polyprotein), is critical for the diabetogenicity of EMC virus. The G base at the nucleotide position 3155 (Ala[GCC]776 in the polyprotein) is unique to all diabetogenic variants, whereas the A base at the same position (Thr[ACC]776 in the polyprotein) is identical to all nondiabetogenic variants. A single-point mutation (G to A; Ala to Thr) results in the conversion of the diabetogenic variant into a nondiabetogenic variant of EMC virus. On the basis of these observations, we conclude that a single amino acid, Ala776, on the polyprotein of EMC virus appears responsible for the inducement of diabetes in susceptible mice. Conversion of Ala776 into Thr776 on the polyprotein by a point mutation, G to A at the nucleotide position 3155, results in the loss of diabetogenicity.
Diabetes 1993 Mar
PMID:Determination of diabetogenicity attributable to a single amino acid, Ala776, on the polyprotein of encephalomyocarditis virus. 838 54


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