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

Cytokine effects on permanent cell lines of transformed mouse pancreatic alpha- and beta-cells were compared. The beta-tumor cell 1 (beta TC1) line (from an adenoma created in transgenic mice expressing the SV40 large T-antigen oncogene under control of the rat insulin II promoter) produced insulin predominantly, although small quantities of intracellular glucagon (100:1 insulin to glucagon) were detectable by radioimmunoassay. The alpha TC1 line (from an adenoma created in transgenic mice expressing the SV40 large T-antigen oncogene under control of the rat preproglucagon promoter) produced not only glucagon but also considerable quantities of insulin (4:1 glucagon to insulin) and preproinsulin mRNA. We therefore cloned alpha TC1 cells and obtained 12 glucagon-producing clonal cell lines that did not produce levels of insulin detectable by radioimmunoassay. Analysis by Northern blotting of total RNA from two lines, alpha TC1 clones 6 and 9, confirmed the absence of preproinsulin mRNA. No somatostatin or pancreatic polypeptide was detected by immunohistochemical staining in alpha TC1 clones 6 or 9 or beta TC1 cells. Rat recombinant gamma-interferon (IFN-gamma; 5-250 U/ml) or mouse recombinant interleukin 1 (IL-1; 1-25 U/ml) individually inhibited DNA synthesis in beta TC1 cells after 3 days of treatment. The two cytokines in combination acted synergistically to further depress DNA synthesis and increase cytotoxicity. In contrast, alpha TC1 clone 9 cells were not sensitive to inhibition of DNA synthesis by each cytokine individually, although glucagon synthesis was inhibited. The combination of these cytokines caused marked inhibition of DNA and glucagon syntheses in alpha TC1 clone 9 cells. alpha TC1 clone 9 cells were somewhat more resistant to the cytotoxic action of the combined cytokines than were beta TC1 cells. Incubation with 50 U/ml IFN-gamma induced class II MHC molecules (I-Ab, I-Ad, and I-Ed) and enhanced the constitutive expression of class I molecules (H-2Kb and H-2Kd) on the cell surfaces of beta TC1, uncloned alpha TC1, and alpha TC1 clones 6 and 9. Thus, these cell lines are heterozygous for MHC alleles derived from both parental strains used in the construction of the transgenic mice [C57BL/6J (H-2b) and DBA/2J (H-2d)]. Class II gene transcription induced by IFN-gamma was confirmed in beta TC1 and alpha TC1 clone 9 cells by Northern blot analysis with A alpha-, A beta-, E alpha, and E beta-DNA probes.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1990 Apr
PMID:Comparison of cytokine effects on mouse pancreatic alpha-cell and beta-cell lines. Viability, secretory function, and MHC antigen expression. 210 69

B10.BR, DBA/2, and BALB/c by J mice were infected with Trypanosoma brucei rhodesiense (Lou Tat clone 1). Subsequent infection with the D variant of encephalomyocarditis virus (EMC-D) resulted in no diabetes or encephalitis, even in the susceptible DBA/2 and BALB/c by J strains. Low levels of circulating interferon (IFN) were detected in trypanosome-infected mice at the time of EMC-D infection. All strains were severely immunosuppressed as a result of trypanosome infection, as evidenced by decreased virus-specific neutralizing antibody titers, compared to virus-infected controls. We attempted to simulate some aspects of T.b. rhodesiense infection in B10.BR mice by pretreating mice with cyclophosphamide and IFN prior to EMC-D infection. Immunosuppression by cyclophosphamide greatly enhanced the pathogenesis of EMC-D, while IFN protected against the diabetogenic effect of this virus. Our results indicate that: (i) T.b. rhodesiense infection inhibited EMC-D-induced diabetes, (ii) this inhibition was not due solely to the immunosuppression generated by the trypanosome infection, and (iii) IFN generated by the trypanosome infection could play some protective role in the inhibition of EMC-D-induced diabetes by trypanosome infection.
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PMID:Trypanosoma brucei rhodesiense infection in mice prevents virus-induced diabetes: possible role of interferon and immunological mechanisms. 243 62

We examined the clinical usefulness determined by polyacrylamide gel electrophoresis, followed by reaction with peroxidase-coupled lectins using urinary glycoproteins for diabetic nephropathy in 20 patients with diabetes mellitus. Lectins used were Triticum vulgaris (WGA), Phaseolus vulgaris (PHA-E4), Dolichos biflorus (DBA), and Lens culinaris (LCA), which have high affinity for beta 1----4N-acetyl-D-glucosamine (GlcNAc beta 1----4GlcNAc), N-acetyl-D-galactosamine (GalNAc), alpha-galactosamine (alpha-GalNAc), and alpha-mannose (alpha-Man) residues, respectively. Electrophoretic patterns of urinary glycoproteins clearly showed the presence of lectin-reactive glycoproteins with molecular weights lower than that of albumin. The molecular weight of the main bands reacted with WGA, PHA-E4 or LCA were 50,000 and 38,000, and increased with the progress of diabetic nephropathy. WGA reacted strongly with many glycoproteins having a wide range of molecular weights. LCA and PHA-E4 reacted preferentially with glycoproteins of molecular weights glycoproteins of molecular weights lower than 50,000, but no reaction was observed by DBA. These results suggest that low molecular urinary glycoproteins have abundant carbohydrate residues such as GlcNAc beta 1----4GlcNAc, GalNAc, and alpha-Man. The excretion of low molecular weight glycoproteins with high affinities for some lectins suggests functional impairment in diabetic nephropathy.
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PMID:[Electrophoretic analysis of urinary glycoproteins in diabetic nephropathy using peroxidase-lectins]. 248 79

Elimination or inactivation of lymphoid tissue in the pancreatic islet preparation achieves prolongation of islet-allograft survival. In this study we examined the effect of gamma-irradiation on mouse islet-allograft survival. In a B6AF1 isograft model, irradiation up to 2400 rad did not induce deterioration of islet function over 200 days, but greater doses caused cessation of graft function between 83 and 186 days. When DBA/2 crude islets were transplanted into B6AF1 recipients, all nonirradiated allografts were acutely rejected. Marked prolongation of allograft survival was achieved by islet irradiation with doses between 800 and 12,000 rad. With higher doses, significant numbers of allografts survived beyond the controls, but many lost function between 78 and 180 days, with none surviving greater than 200 days. Irradiation with 16,000 rad caused acute radiation damage. Because most secondary islet allografts in recipient mice that lost primary islet-graft function between 84 and 195 days survived greater than 100 days, late functional loss was probably due to the radiation injury. Combined use of recipient treatment with cyclosporin A and graft irradiation (2400 rad) achieved prolongation of DBA/2 islets in B6AF1 mice.
Diabetes 1989 Jan
PMID:Effect of gamma-irradiation on mouse pancreatic islet-allograft survival. 249 98

A murine mixed islet-lymphocyte coculture system (MILC) was used to quantitate the immunogenicity of a pure population of pancreatic beta-cells to more clearly define whether stimulator major histocompatibility complex (MHC) class II-positive dendritic cells are a major component leading to islet immunogenicity. Pancreatic beta-cells express MHC class I antigen but not class II antigen. These experiments compared the in vitro immunogenicity of fluorescence-activated cell sorted (FACS-IV) pure beta-cells (MHC class I-positive cells only) relative to unpurified dispersed islet cells (MHC class I-positive cells and class II-positive cells). The results demonstrated the surprising finding that pure DBA/2J (H-2d) pancreatic beta-cells stimulated a strong cytotoxic T-lymphocyte (CTL) response when exposed to C57BL/6 (H-2b) allosplenocytes in the MILC, similar to DBA/2J nonpurified dispersed islet cells. Furthermore, the stimulation of CTL by both purified beta-cells and nonpurified dispersed islet cells was blocked by addition of MHC-specific anti-class I monoclonal antibody directed against stimulator MHC antigen. The data imply that the highly immunogenic MHC class II-positive passenger leukocytes present in the islets were not necessary for the generation of the immune response in the presence of MHC class I-positive beta-cells. Although most of the pretreatment regimens attempting to decrease islet immunogenicity have been directed at eliminating the MHC class II-positive passenger leukocytes from the islets, this work suggests that modulation of MHC class I antigen may be an important approach.
Diabetes 1989 Jan
PMID:Generation of allospecific cytolytic T-lymphocytes stimulated by pure pancreatic beta-cells in absence of Ia+ dendritic cells. 264 43

Iron-chelating treatment is indicated in all children on prolonged transfusion therapy (i.e., chiefly patients with thalassemia and Blackfan-Diamond anemia). The purpose of iron-chelating treatment is to prevent the development of manifestations of iron overload including cardiac hemosiderosis and insulin-dependent diabetes mellitus (which are two potentially fatal complications), hepatic cirrhosis, hypoparathyroidism, hypothyroidism, and delayed puberty. Deferoxamine is the only effective iron-chelating agent and should be given in a daily dose of 40 mg/kg at initiation of the transfusion program. Administration is by subcutaneous infusions from 8 to 10 hours per day. The goal of iron-chelating treatment is to maintain serum ferritin levels between 500 and 1,000 ng/ml. This long-term treatment is a significant burden for patients and it can be hoped that non-toxic iron-chelating agents, active by mouth, will become available.
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PMID:[Iron chelation in children]. 268 51

Iron chelation therapy must be associated with the regular blood transfusions required for thalassaemia and other chronic anemias. We report here a study concerning 4 groups of patients, aged 6 to 28, regularly transfused at Necker Enfants-Malades hospital: a) 20 with thalassaemia major; b) 6 with thalassaemia intermedia; c) 2 with sickle cell disease and d) 2 with Blackfan-Diamond syndrome. The transfusion regimen consisting of monthly or quarterly transfusions varied as a function of the groups. Desferal was used in all patients. The dosage and the route of administration (IV, IM, SC) were adapted to the amount of iron transfused and to the nature of the disease. The serum ferritin level was considered as the indicator of the iron overload. Comparisons were established between the quantities of iron transfused, ferritin levels, and parameters such as dosage, route of administration and compliance to Desferal. During the period of study 3 patients died from cardiac failure due to transfusional hemosiderosis. Endocrine complications (diabetes 2 cases, hypocalcemia 3 cases, hypothyroidism 1 case and delayed puberty 7 cases) were observed. This high incidence of complications induced by post-transfusional iron overload has recently prompted us to improve the quality of chelation therapy through the use of the services of a specialized center where patients as well as their families can be trained more adequately in home care and self-treatment.
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PMID:[Treatment of post-transfusion iron overload by deferoxamine]. 273 4

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

Studies of diabetogenic properties of Coxsackie A13 and B4 viruses in mice sensitive to diabetes (males, DBA line) and resistant (males and females F1(CBA X C57BL/6), females DBA/2 using in the latter case the subdiabetogenic doses of alloxan revealed in the infected animals biochemical changes manifested by reduction of glucose tolerance and disorders in the synthesis of immunoreactive insulin. Most marked changes were observed in males of DBA/2 line infected with Coxsackie B4 virus and in males F1 (CBA X C57BL/6) and females DBA/2 infected with Coxsackie A14 virus. With Coxsackie A13 virus such data have been obtained for the first time.
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PMID:[Diabetogenic properties of Coxsackie A13 and Coxsackie B4 viruses in experimental infection in mice]. 284 68

Histopathological examinations were carried out on female DBA/2N and CD-1 mice which were autopsied 4 and 12 weeks after six daily intraperitoneal injections of streptozotocin (SZ). Histopathological changes related to SZ treatment were found in the pancreas, liver and kidneys. Little difference was observed between the two strains in the histological changes of the pancreas (a decrease in size of the islets, and degranulation and a decrease in the number of B cells) and liver (hypertrophy of hepatocytes and cytoplasmic invagination into hepatocyte nuclei). With regard to the changes in the kidneys, DBA/2N mice showed characteristic inclusions positive to periodic acid-Schiff reagent in the distal tubule epithelial cells, while CD-1 mice showed remarkable luminal dilatation and epithelial cell deformation of distal tubules. SZ-induced diabetes had no influence on the development of spontaneous cardiovascular lesions in DBA/2N mice under the present experimental conditions.
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PMID:Histopathology of streptozotocin-induced diabetic DBA/2N and CD-1 mice. 294 65


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