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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-dependent diabetes mellitus (IDDM) is generally believed to be an autoimmune disease resulting from T-cell dysfunction that produces beta-cell damage, but it is conceivable that some forms of IDDM are not immunologically mediated. The effect of the expression of a foreign transgenic MHC class I antigen (H-2Kb), restricted to pancreatic islet beta-cells, was tested in vitro and in nude (athymic) mice to determine whether beta-cell dysfunction was due to non-immune mechanisms. The models used clearly excluded immune involvement in beta-cell damage. Fetal pancreas from transgenic and littermate control mice was maintained in organ culture for up to 18 days and insulin secretion into the medium assessed. For the initial 3-4 days in vitro, fetal control and transgenic pancreas secreted similar amounts of insulin, but thereafter insulin secretion by the transgenic tissue decreased in comparison with the controls. When the cultured pancreas was transplanted into nude mice, the transgenic issue produced smaller grafts than the control pancreas, but there was wide variation in graft size. Expression of H-2Kb antigens in beta-cells of nude transgenic mice also resulted in early-onset diabetes. The insulin content in the pancreas of young H-2Kb transgenic euthymic mice, (previously shown not to have insulitis), was reduced but glucagon content was normal. The reduction in in vivo insulin production was similar chronologically to the reduced insulin production by transgenic islets in vitro. These data confirm the non-immune loss of beta-cell function in MHC-transgenic mice and they may be a model for atypical Type I diabetes.
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PMID:Inherent beta-cell dysfunction induced by transgenic expression of allogeneic major histocompatibility complex class I antigen in islet cells. 166 46

The pathogenesis of type 1 diabetes involves autoimmune processes directed against the pancreatic beta-cells. The etiology is not known, but circumstantial evidence suggests a connection between virus infection and development of the disease. Therefore, because the interferon-(IFN) dependent 2',5'-oligoadenylate (2-5A) synthetase system constitutes an important part of the nonspecific immune defense against viral infections, the activity of the enzyme was examined in islets of Langerhans, RIN cells, and GH3 cells. First, the 2-5A synthetase was expressed constitutively in all cell types and, second, all cells were sensitive to stimulation with IFN-alpha. The 2-5A synthetase activity induced by 1,000 U/ml of IFN-alpha increased by 400% in pancreatic islets and by more than 1000% in GH3 and RIN cells. However, the IFN-alpha concentration needed to induce half-maximal 2-5A synthetase activity was nearly the same in the three cell types (i.e., ranging from 59 to 66 U/ml IFN-alpha). The 2-5A synthetase present in islets and RIN cells was highly sensitive to poly (I:C). In pancreatic islets and RIN cells, the 2-5A synthetase enzyme generated dimers and trimers of 2',5'-oligoadenylates. Furthermore, exposure of RIN cells to IFN-alpha showed an increase in MHC class I expression already at 5 U/ml and maximal expression at about 200 U/ml IFN-alpha. The examined endocrine cells express the 2-5A synthetase enzyme as well as MHC class I antigen constitutively, but also by stimulation with IFN in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon stimulates the expression of 2',5'-oligoadenylate synthetase and MHC class I antigens in insulin-producing cells. 172 88

It is well established that insulin-dependent diabetes (IDDM) is an autoimmune disease with a strong genetic link to the HLA locus. It is less well understood, however, how the destruction of the insulin-producing beta cells is effected and why neighboring non-beta islet cells are spared. Also incompletely explained are the observations that, unlike other autoimmune diseases such as multiple sclerosis, IDDM does not preferentially affect females, the incidence of the disease is highest among young adults, and there are temporal correlations between the onset of the disease and emotional trauma. We have addressed some of these questions by using transgenic mice that constitutively express the MHC class I antigen Dd in the beta cells of the pancreas. Although both male and female Ins.Dd mice expressed equivalent amounts of the Dd protein only the males developed diabetes. The diabetes in the males could be reversed by castration, and the normoglycemic females became diabetic following either ovariectomy and the implantation of a slow-release pellet containing testosterone or the inclusion of dexamethasone in the drinking water. In contrast, transgenic mice that expressed the herpes simplex virus type 1 glycoprotein D in the pancreatic beta cells were normoglycemic and showed no obvious histopathological consequences. The observation that the beta-cell dysfunction by the increased expression of the MHC class I protein Dd cannot be induced by the herpes viral protein suggests that the cellular damage is related to a specific structure or function of the MHC proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Male-specific beta-cell dysfunction and diabetes resulting from increased expression of a syngeneic MHC class I protein in the pancreata of transgenic mice. 196 48

MHC class I antigen expression was found to be low on the lymphocytes of patients with insulin dependent diabetes mellitus (IDDM). Thus, it has been proposed that the defective expression of MHC antigens could lead to faulty immunological responses with the eventual destruction of the pancreatic beta cells. The objective in this study was to compare MHC antigen expression in IDDM patients and their presently healthy siblings. Nineteen children (mean age 10.8 +/- 3.9 years) with diabetes and their 25 siblings (mean age 10.7 +/- 4.6 years) were enrolled in the study. Peripheral blood lymphocytes isolated from venous blood samples were incubated with FITC conjugated monoclonal antibody W6/32. The amount of antibody binding by cell surface MHC class I antigens was assessed by flow cytometry. MHC class I molecule expression did not differ significantly among IDDM patients and their siblings. It was concluded that MHC class I antigen expression did not appear to be indicative of a susceptibility to develop autoimmune diabetes.
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PMID:MHC class I antigen expression in patients with IDDM and their siblings. 936 65