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Karsten Buschard - One of the best experts on this subject based on the ideXlab platform.

  • Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice.
    Journal of diabetes research, 2015
    Co-Authors: Dina Silke Malling Damlund, Karsten Buschard, Stine Broeng Metzdorff, Jane Preuss Hasselby, Maria Wiese, Mia Thorup Lundsager, Dennis Sandris Nielsen, Axel Kornerup Hansen, Hanne Frøkiær
    Abstract:

    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in Mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD Mice are lacking. We hypothesized that NOD Mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn Mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND) 1–4 in NOD Mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD Mice whereas neonatal C57BL/6 Mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD Mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 Mice.

  • Linomide does not prevent spontaneous autoimmune thyroiditis in NOD Mice.
    Autoimmunity, 2001
    Co-Authors: M.-l. Hartoft-nielsen, Karsten Buschard, Anne Kaas, Troels Bock, A. K. Rasmussen, Ulla Feldt-rasmussen
    Abstract:

    Linomide is a potent immunomodulator and has been reported to prevent type 1 diabetes mellitus in non-obese diabetic (NOD) Mice and to reduce the incidence of other autoimmune diseases in animal models. The mechanisms of action seem to involve antigen expression by down regulation of macrophage activity and to antagonise the activation of Th1 cells during the cellular immune response. With the purpose to investigate the effect of Linomide on the incidence of spontaneous autoimmune thyroiditis (AIT) in female NOD Mice we administered Linomide in drinking water (100 mg/kg/day) to NOD Mice from 5th to 19th week of age. The Mice were sacrificed at the end of week 19. None of the Mice developed diabetes during the study period. The incidence of thyroiditis was evaluated on paraffin HE-stained sections and graduated on a scale from 0 to 4. Thirty-two percent of 37 Mice treated with Linomide developed thyroiditis compared to 45% of 22 controls (p=0.31, ±2=1.00). Among the Mice who developed thyroiditis no differ...

  • Gluten-free diet prevents diabetes in NOD Mice.
    Diabetes metabolism research and reviews, 1999
    Co-Authors: David P. Funda, Anne Kaas, Troels Bock, Helena Tlaskalova-hogenova, Karsten Buschard
    Abstract:

    Background Epidemiological as well as animal studies have shown that environmental factors such as nutrition contribute to the development of diabetes. In this study we investigated whether the early introduction of a gluten-free diet can influence the onset and/or incidence of diabetes, as well as insulitis and the number of gut mucosal lymphocytes, in non-obese diabetic (NOD) Mice. Methods Gluten-free and standard Altromin diets (with the same milk protein and vitamin content) were given to breeding pairs of NOD Mice as well as to the first generation of NOD female Mice, which were then observed for 320 days. Results A substantially lower diabetes incidence (χ2=15.8, p=0.00007) was observed in NOD Mice on the gluten-free diet (15%, n=27) compared to Mice on the standard diet (64%, n=28). In addition, Mice on the gluten-free diet developed diabetes significantly later (244±24 days SEM) compared to those on the standard diet (197±8 days, p=0.03). No differences in the number of CD3+, TCR-γδ+, IgA+, and IgM+ cells in the small intestine were observed. Conclusion We showed that gluten-free diet both delayed and to a large extent prevented diabetes in NOD Mice that have never been exposed to gluten. Copyright © 1999 John Wiley & Sons, Ltd.

  • Cytokine production in NOD Mice on prophylactic insulin therapy
    APMIS : acta pathologica microbiologica et immunologica Scandinavica, 1999
    Co-Authors: E Strandell, Karsten Buschard, Anne Kaas, Troels Bock, Marie-louise Hartoft-nielsen, Klaus Bendtzen
    Abstract:

    We investigated whether cytokines produced primarily by monocytes/macrophages (IL-1alpha), Th1-lymphocytes (IFNgamma), or Th2-lymphocytes (IL-4) are modulated in diabetes-prone NOD Mice by insulin treatment as used in prophylaxis studies. The cytokines were measured by ELISA in plasma and in supernatants of spleen cells activated ex vivo by lipopolysaccharide plus phytohemagglutinin. Insulin, 0.25-0.50 IU/day, was given subcutaneously for 8 weeks starting in 4-week-old female Mice. The insulin-treated and control NOD Mice showed similar weight gains and, by the end of the study, both groups exhibited cell infiltration in about 25% of their islets. IL-1alpha, IFNgamma and IL-4 were generally below detection in plasma of prediabetic animals and controls. Diabetic NOD Mice, aged 28-45 weeks, had significantly elevated plasma IL-1alpha: 154+/-39 pg/ml (mean+/-SEM, p

  • Age-related changes in Tγδ cells of NOD Mice
    Immunology letters, 1995
    Co-Authors: David P. Funda, Jens Peter Stenvang, Karsten Buschard
    Abstract:

    Abstract Tγδ cells have been reported to recognize both mycobacterial and human heat-shock proteins (HSP), and a possible role of 65 kDa HSP has been suggested also in the pathogenesis of insulin-dependent diabetes mellitus. The aim of this study was to investigate age-related changes of Tγδ cells during diabetes development in non-obese diabetic (NOD) Mice. Using FACS analysis relative numbers of T γδ + cells from thymus, blood and spleen were determined in 3-week-old non-diabetic, at onset of diabetes, and 1-week diabetic NOD Mice and corresponding BALB/cJ controls. In comparison to BALB/cJ Mice, higher values (2.4 ± 0.2% vs. 1.1 ± 0.1%) were found in the thymus of 3-week-old NOD Mice ( P P P P + subset of mononuclear cells. Thus, our results show relatively higher numbers of Tγδ cells in NOD Mice and their increase in the periphery at onset of diabetes and later may suggest that Tγδ cells participate in β-cell destruction.

Stellan Sandler - One of the best experts on this subject based on the ideXlab platform.

  • Elevated glucagon-like peptide-1 plasma levels, as a possible adaptive response, in diabetic NOD Mice
    Biochemical and biophysical research communications, 2012
    Co-Authors: Tobias Rydgren, Andreas Börjesson, Annika Carlsson, Stellan Sandler
    Abstract:

    Abstract The incretin glucagon-like peptide-1 (GLP-1) and other GLP-1 receptor agonists have been shown to cause both antiapoptotic as well as regenerative effects on beta-cells in different animal models for diabetes. Our aim of this study was to test the hypothesis that spontaneously diabetic non obese diabetic (NOD) Mice show an altered expression of GLP-1 compared to normoglycemic age-matched controls as a consequence of a diabetic state. To do this we used an ELISA prototype for mouse GLP-1 to measure plasma total GLP-1 from recently diabetic NOD Mice as well as from age-matched normoglycemic NOD Mice (controls). We also stained sections of pancreatic glands for GLP-1 from diabetic NOD Mice and controls. We found increased levels of plasma total GLP-1 in diabetic NOD Mice, when compared to control Mice, both from non-fasted Mice and from Mice fasted for 2 h. Furthermore, diabetic NOD Mice displayed a higher GLP-1 response to an oral glucose tolerance test, compared to control Mice. We also found that sections of pancreatic glands from diabetic NOD Mice had an increased GLP-1 positive islet area in regard to relative islet area (i.e. total islet area / total pancreas area of the sections) compared to control Mice. To our knowledge, this study is the first to show increased levels of GLP-1 in plasma in spontaneously diabetic NOD Mice. We suggest that these results might represent a compensatory mechanism of the diabetic NOD Mice to counteract beta-cell loss and hyperglycemia.

  • Early prophylaxis with recombinant human interleukin-11 prevents spontaneous diabetes in NOD Mice.
    Diabetes, 1999
    Co-Authors: Ferdinando Nicoletti, P. Zaccone, Ignacio Conget, Ramon Gomis, Klaus Bendtzen, Christer Möller, Pier Luigi Meroni, William L. Trepicchio, Stellan Sandler
    Abstract:

    We evaluated the effects of recombinant human (rh) interleukin (IL)-11 on the development of spontaneous and cyclophosphamide-induced diabetes in female NOD Mice. Prolonged treatment with rhIL-11 10 microg i.p. five consecutive times a week between the 4th and 22nd weeks of age significantly suppressed both development and cumulative incidence of type 1 diabetes. Disease protection was transient because most of the animals developed type 1 diabetes within 3 months of treatment withdrawal. In contrast, rhIL-11 failed to prevent type 1 diabetes when administered for the first time to euglycemic 18-week-old NOD Mice. Most likely, this discrepancy was not due to age-dependent differences in the immunological responses of NOD Mice to rhIL-11 because staphylococcus aureus enterotoxin B-induced tumor necrosis factor (TNF) and IL-12 production were equally suppressed by rhIL-11 in 12- and 25-week-old NOD Mice. Relative to controls, NOD Mice pretreated with rhIL-11 also showed significantly diminished blood levels of TNF, interferon-gamma, and IL-12 induced by anti-CD3 antibody and/or lipopolysaccharide. The results demonstrate that rhIL-11 has powerful anti-inflammatory effects that are capable of down-regulating early immuNODiabetogenic pathways in NOD Mice.

Troels Bock - One of the best experts on this subject based on the ideXlab platform.

  • Linomide does not prevent spontaneous autoimmune thyroiditis in NOD Mice.
    Autoimmunity, 2001
    Co-Authors: M.-l. Hartoft-nielsen, Karsten Buschard, Anne Kaas, Troels Bock, A. K. Rasmussen, Ulla Feldt-rasmussen
    Abstract:

    Linomide is a potent immunomodulator and has been reported to prevent type 1 diabetes mellitus in non-obese diabetic (NOD) Mice and to reduce the incidence of other autoimmune diseases in animal models. The mechanisms of action seem to involve antigen expression by down regulation of macrophage activity and to antagonise the activation of Th1 cells during the cellular immune response. With the purpose to investigate the effect of Linomide on the incidence of spontaneous autoimmune thyroiditis (AIT) in female NOD Mice we administered Linomide in drinking water (100 mg/kg/day) to NOD Mice from 5th to 19th week of age. The Mice were sacrificed at the end of week 19. None of the Mice developed diabetes during the study period. The incidence of thyroiditis was evaluated on paraffin HE-stained sections and graduated on a scale from 0 to 4. Thirty-two percent of 37 Mice treated with Linomide developed thyroiditis compared to 45% of 22 controls (p=0.31, ±2=1.00). Among the Mice who developed thyroiditis no differ...

  • Gluten-free diet prevents diabetes in NOD Mice.
    Diabetes metabolism research and reviews, 1999
    Co-Authors: David P. Funda, Anne Kaas, Troels Bock, Helena Tlaskalova-hogenova, Karsten Buschard
    Abstract:

    Background Epidemiological as well as animal studies have shown that environmental factors such as nutrition contribute to the development of diabetes. In this study we investigated whether the early introduction of a gluten-free diet can influence the onset and/or incidence of diabetes, as well as insulitis and the number of gut mucosal lymphocytes, in non-obese diabetic (NOD) Mice. Methods Gluten-free and standard Altromin diets (with the same milk protein and vitamin content) were given to breeding pairs of NOD Mice as well as to the first generation of NOD female Mice, which were then observed for 320 days. Results A substantially lower diabetes incidence (χ2=15.8, p=0.00007) was observed in NOD Mice on the gluten-free diet (15%, n=27) compared to Mice on the standard diet (64%, n=28). In addition, Mice on the gluten-free diet developed diabetes significantly later (244±24 days SEM) compared to those on the standard diet (197±8 days, p=0.03). No differences in the number of CD3+, TCR-γδ+, IgA+, and IgM+ cells in the small intestine were observed. Conclusion We showed that gluten-free diet both delayed and to a large extent prevented diabetes in NOD Mice that have never been exposed to gluten. Copyright © 1999 John Wiley & Sons, Ltd.

  • Cytokine production in NOD Mice on prophylactic insulin therapy
    APMIS : acta pathologica microbiologica et immunologica Scandinavica, 1999
    Co-Authors: E Strandell, Karsten Buschard, Anne Kaas, Troels Bock, Marie-louise Hartoft-nielsen, Klaus Bendtzen
    Abstract:

    We investigated whether cytokines produced primarily by monocytes/macrophages (IL-1alpha), Th1-lymphocytes (IFNgamma), or Th2-lymphocytes (IL-4) are modulated in diabetes-prone NOD Mice by insulin treatment as used in prophylaxis studies. The cytokines were measured by ELISA in plasma and in supernatants of spleen cells activated ex vivo by lipopolysaccharide plus phytohemagglutinin. Insulin, 0.25-0.50 IU/day, was given subcutaneously for 8 weeks starting in 4-week-old female Mice. The insulin-treated and control NOD Mice showed similar weight gains and, by the end of the study, both groups exhibited cell infiltration in about 25% of their islets. IL-1alpha, IFNgamma and IL-4 were generally below detection in plasma of prediabetic animals and controls. Diabetic NOD Mice, aged 28-45 weeks, had significantly elevated plasma IL-1alpha: 154+/-39 pg/ml (mean+/-SEM, p

  • Reduction of diabetes incidence in NOD Mice by neonatal glucose treatment
    APMIS : acta pathologica microbiologica et immunologica Scandinavica, 1991
    Co-Authors: Troels Bock, Troels W. Kjaer, M. Jørgensen, Knud Josefsen, Jørgen Rygaard, Karsten Buschard
    Abstract:

    The aim of this study was to investigate whether neonatal glucose treatment influences the incidence of diabetes in NOD Mice. Thirty-nine NOD Mice (19 males, 20 females) were treated with 8 g glucose/kg BW/day administered by subcutaneous injections twice a day for the first six days of life. Thirty-six untreated NOD Mice (20 males, 16 females) served as a control group. In the glucose-treated group, 33% became diabetic compared with 58% in the control group (X2 = 5.3, p = 0.021). Among the glucose-treated males, 16% became diabetic compared with 50% of the untreated males (X2 = 5.5, p = 0.019), whereas 50% of the glucose-treated females became diabetic compared with 69% of the untreated females (X2 = 1.1, NS). We conclude that neonatal glucose treatment can reduce the diabetes incidence in NOD Mice. These results could have implications for the prevention of type 1 diabetes mellitus in humans.

Rex Neal Smith - One of the best experts on this subject based on the ideXlab platform.

  • Effects of streptozotocin on autoimmune diabetes in NOD Mice.
    Clinical and experimental immunology, 2003
    Co-Authors: Maria Koulmanda, A. Qipo, Hugh Auchincloss, Rex Neal Smith
    Abstract:

    Non-obese diabetic (NOD) Mice develop autoimmunity that destroys their native beta cells causing diabetes. Their autoimmunity will also destroy syngeneic transplanted islets and transfer both autoimmunity and diabetes via spleen cells to non-diabetic Mice. In this report, we studied the effects of streptozotocin (STZ) on the autoimmune diabetes in NOD Mice. We transplanted NOD.SCID islets into three groups of NOD Mice: (1) spontaneously diabetic NOD Mice (NOD-sp.); (2) prediabetic NOD Mice made diabetic by streptozotocin (NOD-stz); and (3) diabetic NOD Mice also treated with streptozotocin (NOD-sp./stz). In the first group, the transplants were rejected within 3 weeks. In the second and third groups, the transplants survived indefinitely. Alloxan, a drug similar to streptozotocin, did not have the same effect as streptozotocin. The ability of streptozotocin to prevent diabetes in young NOD Mice was reversed by anti-CD8 antibody treatment but not by anti-CD4 treatment. Streptozotocin also made spleen cells from diabetic NOD Mice less effective transferring diabetes. These results indicate that streptozotocin treatment both prevents and reverses the islet destructive autoimmunity in NOD Mice. We postulate that the effects of streptozotocin treatment may be mediated in part by regulatory T cells.

Chantal Mathieu - One of the best experts on this subject based on the ideXlab platform.

  • Unaltered Diabetes Presentation in NOD Mice Lacking the Vitamin D Receptor
    Diabetes, 2007
    Co-Authors: Conny Gysemans, Evelyne Van Etten, Lutgart Overbergh, Annapaula Giulietti, Guy Eelen, Mark Waer, Annemieke Verstuyf, Roger Bouillon, Chantal Mathieu
    Abstract:

    OBJECTIVE— Vitamin D deficiency increases risk for type 1 diabetes in genetically predisposed individuals, while high doses of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] prevent insulitis and diabetes in NOD Mice. RESEARCH DESIGN AND METHODS— Since 1,25(OH) 2 D 3 regulates gene transcription through the vitamin D receptor (VDR), we investigated the role of VDR in diabetes development by creating NOD Mice without functional VDR. RESULTS— VDR −/− NOD Mice are rachitic and have lower numbers of putative regulator cells [TCR-α/β + CD4 − CD8 − (natural killer T-cells) and CD4 + CD25 + T-cells [in central and peripheral immune organs compared with VDR +/+ NOD littermates. Lipopolysaccharide-stimulated VDR −/− NOD macrophages expressed lower interleukin (IL)-1, IL-6, and CC chemokine ligand 2 mRNA, correlating with less nuclear translocation of p65 nuclear factor-κB compared with VDR +/+ NOD macrophages. Thymic and lymph NODe dendritic cells from VDR −/− NOD Mice displayed an even less mature CD11c + CD86 + phenotype than VDR +/+ NOD Mice. Despite this immune phenotype linked to diabetes in NOD Mice, VDR −/− NOD Mice developed insulitis and diabetes at the same rate and incidence as VDR +/+ NOD littermates. CONCLUSIONS— Despite aggravating known immune abnormalities in NOD Mice, disruption of VDR does not alter disease presentation in NOD Mice in contrast to the more aggressive diabetes presentation in vitamin D–deficient NOD Mice.

  • Acute Shock Induced by Antigen Vaccination in NOD Mice
    Diabetes, 2003
    Co-Authors: Lutgart Overbergh, Roger Bouillon, Brigitte Decallonne, Dumitru Branisteanu, Dirk Valckx, Ahmad Kasran, Chantal Mathieu
    Abstract:

    Type 1 diabetes in NOD Mice can be prevented through autoantigen vaccination by shifting lymphocyte differentiation toward a T-helper 2 (Th 2 ) response. However, in other models of autoimmunity, this approach may be accompanied by unexpected triggering of Th 2 -dependent anaphylactic shock. To test the safety of vaccination therapy in the NOD mouse model, we evaluated the effects of immunization with a wide battery of antigens in NOD, BALB/c, and C57BL/6 Mice. Surprisingly, a nondiabetogenic antigen, hen egg white lysozyme, induced severe shock exclusively in NOD Mice (shock in 11 of 11 Mice, lethal in 3 Mice). Shock severity was further increased by a more pronounced Th 2 setting generated by 1α,25(OH) 2 D 3 administration (17 of 17 Mice, lethal in 14 Mice, P 1 /Th 2 cytokine profile analysis showed that the shock phenomenon was paralleled by a Th 2 response. mRNA expression of platelet-activating factor receptor (PAF-R) was significantly higher in NOD Mice ( P 2 D 3 . Pretreatment with WEB2086 (PAF-R antagonist) again protected all Mice from lethal shock, indicating PAF as an anaphylaxis effector. In conclusion, in NOD Mice, vaccination leading to a Th 2 immune shift can result in a lethal anaphylactic reaction.

  • prevention of autoimmune diabetes in NOD Mice by 1 25 dihydroxyvitamin d3
    Diabetologia, 1994
    Co-Authors: Chantal Mathieu, Mark Waer, Jozef Laureys, Omer Rutgeerts, Roger Bouillon
    Abstract:

    1,25 dihydroxyvitamin D3, the active form of vitamin D, has immunomodulatory properties in vitro and in vivo. We report that treatment with 1,25 dihydroxyvitamin D3 (5 μg/kg on alternate days) prevents the development of clinical diabetes in NOD Mice, an animal model of human autoimmune diabetes. Diabetes incidence in female NOD Mice at the age of 200 days was reduced to 8% in the 1,25 dihydroxyvitamin D treated group vs 56% in the control group (p<0.0001). In parallel, treatment with 1,25 dihydroxyvitamin D3 resulted in a complete normalisation of the capacity to induce suppressor mechanisms in an autologous MLR, which is severely depressed in control NOD Mice. The existence of such suppressor cells was confirmed in transfer experiments, whereby cotransfer of splenocytes from 1,25 dihydroxyvitamin D3 treated NOD Mice prevented diabetes transfer by splenocytes from diabetic NOD Mice into irradiated, 6–8-week-old male NOD Mice. Other known immune defects of the NOD Mice, such as defective natural killer cell killing of YAC-1 targets and defective thymocyte activation by anti-CD3 were not corrected. The pharmacological doses of 1,25 dihydroxyvitamin D3 were universally well tolerated as reflected by a normal weight gain of the Mice. Serum calcium was increased (2.5±0.2 vs 2.2±0.2 mmol/l in the control group, P<0.005), whereas osteocalcin levels nearly doubled and bone calcium content was halved. These findings show that 1,25 dihydroxyvitamin D3 can prevent diabetes in NOD Mice, probably through the correction of their defective suppressor function.

  • Prevention of autoimmune diabetes in NOD Mice by 1,25 dihydroxyvitamin D3.
    Diabetologia, 1994
    Co-Authors: Chantal Mathieu, Mark Waer, Jozef Laureys, Omer Rutgeerts, Roger Bouillon
    Abstract:

    1,25 dihydroxyvitamin D3, the active form of vitamin D, has immunomodulatory properties in vitro and in vivo. We report that treatment with 1,25 dihydroxyvitamin D3 (5 μg/kg on alternate days) prevents the development of clinical diabetes in NOD Mice, an animal model of human autoimmune diabetes. Diabetes incidence in female NOD Mice at the age of 200 days was reduced to 8% in the 1,25 dihydroxyvitamin D treated group vs 56% in the control group (p