Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of voltage-gated K+ channels in mAb-defined T cell subsets from normal mice and mice with experimental autoimmune arthritis was studied with the patch-clamp whole-cell recording technique in combination with fluorescence microscopy. CD4+CD8- Th cells from DBA/1 LacJ mice with type II collagen arthritis expressed low levels of type n K+ channels, and CD4-CD8+ T cells (cytotoxic) showed small numbers of type l or n' K+ channels, like their phenotypic counterparts in normal mice. CD4-CD8-Thy-1.2+ (double negative or DN) T cells from the diseased mice, however, displayed an abundance of type l K+ channels compared to DN T cells in normal mice, or mice immunized with CFA. Furthermore, the aberrant expression of type l K+ channels correlated with the presence of active disease. DN T cells from mice with SLE, type-1 diabetes mellitus, and experimental allergic encephalomyelitis, also exhibited a high number of type l K+ channels. These results suggest that expression of numerous type l K+ channels may be a useful marker for DN T cells associated with these autoimmune disorders.
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PMID:CD4-CD8- T cells from mice with collagen arthritis display aberrant expression of type l K+ channels. 197 26

An enzyme-linked immunosorbent assay (ELISA) has been developed to detect antibodies against surface components of rat islet and spleen lymphocytes. Live islet tumor RIN5 AH cells expressing characteristic ganglioside target antigens or rat spleen cells were immobilized onto wells of microtiter polystyrene plates precoated with poly-l-lysine and then incubated with test or normal rat sera. Cell surface-bound antibodies were quantitated after reaction with horseradish peroxidase-conjugated rabbit anti-rat Ig. With this assay, 46% (6/13) of sera from diabetes-prone BB rats and 100% (8/8) of sera from rats treated with complete Freund's adjuvant/streptozotocin (CFA/STZ) prior to immunization with RIN cells had islet cell surface antibodies: 54% (7/13) and 75% (6/8), respectively, were positive for lymphocyte antibodies (defined as the HRP anti-rat Ig binding exceeding the mean + 2SD of control group values). SDS polyacrylamide gel electrophoresis followed by immunoblotting analysis suggested that the islet cell antibodies in sera from the BB and CFA/STZ rats recognized RIN-cell components that were different in their molecular weights. These antigens were not detectable on spleen cells indicating that the ELISA described can be used to quantitate levels of islet cell specific antibodies which possibly reflect beta cell damage with progression to islet degeneration in the rat.
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PMID:Detection of antibodies to islet cell and splenic lymphocytes in diabetes-prone BB and adjuvant-streptozotocin treated Lewis rats by ELISA and immunoblot analysis. 209

Diabetes was induced in BALB/c mice by four injections of a subdiabetogenic dose (40 mg/kg) of streptozotocin in combination with CFA. The treatment increased the plasma glucose from 5.8 +/- 0.1 to 22.1 +/- 1.3 mmol/liter (n = 9). The diabetic animals had circulating islet cell surface antibodies (75%), and a monoclonal islet cell surface IgM antibody, K56aF3, generated from one of the diabetic BALB/c mice, mediated C-Dependent cytotoxicity against insulin-producing cells and inhibited glucose-stimulated insulin release from isolated rat islets. Solid phase assay on thin layer chromatograms showed no binding of the K56aF3 antibody to glycolipids prepared from relevant cells. However, testing against a series of glycolipids of various non-pancreatic origins showed a preferential binding to a nine-sugar glycolipid isolated from human erythrocytes carrying an unusual blood group A determinant (type 3). It is suggested that this mAb may be associated with the development of diabetes following a combination of polyclonal activation and non-diabetogenic doses of streptozotocin.
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PMID:Islet beta-cytotoxic monoclonal antibody against glycolipids in experimental diabetes induced by low dose streptozotocin and Freund's adjuvant. 296 28

The effect of various adjuvants has been investigated on the multi-low-dose (mld) streptozotocin (STZ) model of diabetes in C57BL/6 and CBA mice; diabetes was severe in the former strain. Diabetic levels of glycaemia were not attained in either strain using half the mld STZ dose (sub-mld-STZ). The adjuvants were found to affect the levels of glycaemia variously. Thus, in C57BL/6 mice at mld-STZ, CFA and saponin had no effect, whereas MDP and LPS respectively decreased and increased glycaemia; at sub-mld-STZ, each of the adjuvants increased glycaemia. In CBA mice, at both mld- and sub-mld-STZ, CFA and saponin increased glycaemia; at mld-STZ, MDP caused an initial increase but a later decrease in glycaemia, whereas with sub-mld-STZ only a decrease in glycaemia occurred; at mld-STZ, LPS was toxic in this strain, and had no effect on glycaemia at sub-mld-STZ. In both C57BL/6 and CBA mice, STZ caused a decrease in both spontaneous and PHA-stimulated blastogenesis. This persisted until day 14 in the C57BL/6 strain and until day 28 in the CBA strain. CFA reversed the anergy by day 7 in C57BL/6 mice and by day 14 in CBA mice, but did not improve beta-cell function, since further increments in glycaemia followed, except in mld-STZ C57BL/6 mice. Islet-cell surface antibodies (ICSAs) and cytotoxic islet-cell antibodies (CxICAs) occurred in both strains of mouse. ICSAs were persistent (still present at day 67), but CxICAs were detected only until day 23. The presence of ICSAs and CxICAs during the development of the diabetic state, and of ICSAs during its perpetuation, suggests that they may have a role in its aetiopathology. The lack of a correlation of non-specific T-cell anergy with glycaemia does not exclude a role for antigen-specific T-cell pathogenic processes.
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PMID:The effect of adjuvants on immune function in the multi-low-dose streptozotocin model of murine diabetes. 307 55

Fourteen rats of the spontaneously diabetic BB line were bled from the retroorbital sinus approximately every 10 days. Sera taken from an early age up to 20 days after the onset of overt diabetes were assayed for complement-fixing antibodies against antigens of the surface of islet cells (CFA). Dispersed islet cells from normal Wistar rats prelabeled with 3H-leucine were used as targets. Target cells in suspension were incubated with heat-inactivated rat sera and then, after washing, exposed to guinea pig complement. Cytolytic "injury" was measured by the percentage of labeled cellular proteins released into the medium. Sera from sequential bleedings from eight normal Wistar rats and three rats from a nondiabetic BB subline were assayed to establish basal control cytolytic activity. The mean response +/- SD obtained with all control sera was 7.7 +/- 1.7%. A response exceeding the mean + 3 SD (12.8%) was considered significantly different from the basal value. Thirteen of the fourteen BB rats developed strongly positive sera. The cytolytic activity preceded the onset of overt diabetes. In several rats CFA appeared 4-8 wk preceding diabetes while in other rats CFA appeared 1-2 wk preceding the manifestation of the disease. These results indicate that CFA may contribute to the destruction of pancreatic islets directly or by attracting mononuclear cells.
Diabetes 1984 Jan
PMID:Complement-fixing islet cell antibodies in the spontaneously diabetic BB rat. 636 Jul 70

Arteriosclerotic involvement of the PFA is correlated with diabetes mellitus. While patients without diabetes have disease limited to the PFA orifice and the circumflex vessels of the PFA, patients with diabetes are prone to extensive PFA involvement. Severity of atherosclerosis involving the CFA and SFA was not found to be specifically related to diabetes.
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PMID:Diabetes mellitus and atherosclerotic involvement of the profunda femoris artery. 650 41

Insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice results from selective destruction of pancreatic islet beta-cells following islet infiltration by mononuclear leukocytes. Cytokines produced by islet-infiltrating mononuclear cells may be involved in beta-cell destruction. Therefore, we analyzed cytokine mRNA expression, by reverse-transcriptase PCR (RT-PCR) assay, in mononuclear leukocytes isolated from pancreatic islets of four groups of mice: diabetes-prone female NOD mice; female NOD mice protected from diabetes by injection of CFA at an early age; male NOD mice with a low diabetes incidence; and female BALB/c mice that do not develop diabetes. We found that mRNA levels of IL-1 beta, IL-2, IL-4, IL-10, and IFN-gamma in mononuclear cells from islets of diabetes-prone female NOD mice increased progressively as these cells infiltrated the islets from age 5 wk to diabetes onset (> 13 wk). However, only IFN-gamma mRNA levels were significantly higher in islet mononuclear cells from 12-wk-old diabetes-prone female NOD mice than from less diabetes-prone NOD mice (CFA-treated females, and males) and normal mice (BALB/c). In contrast, IL-4 mRNA levels were lower in islet mononuclear cells from diabetes-prone female NOD mice than from NOD mice with low diabetes incidence (CFA-treated females and males). Splenic cell mRNA levels of IFN-gamma and IL-4 were not different in the four groups of mice. These results suggest that islet beta-cell destruction and diabetes in female NOD mice are dependent upon intra-islet IFN-gamma production by mononuclear cells, and that CFA-treated female NOD mice and male NOD mice may be protected from diabetes development by down-regulation of IFN-gamma production in the islets.
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PMID:IFN-gamma gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice. 772 37

Freund's complete adjuvant (CFA) and BCG vaccine modulate the development of type 1 diabetes in animal models. In non-obese diabetic mice, CFA and BCG significantly reduced the proportion developing diabetes compared with controls. Histological examination showed that autoimmune disease still developed but had been diverted to become nondestructive. In a preliminary trial in 17 newly diagnosed, type 1 diabetic patients, intracutaneous administration of 0.1 mL of BCG 1 mg/mL led to clinical remission in 11 (65%)--by week 4 in 6. Remission has been sustained in 3 for 6-10 months. No side-effects were reported. A double-blind trial of BCG is warranted.
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PMID:Effect of adjuvant therapy on development of diabetes in mouse and man. 790 74

MHC class I and CD8+ cell deficiency have either prevented systemic lupus erythematosus-like disease in mice or enhanced type I diabetes in nonobese diabetic mice. To study the involvement of MHC class I and class I-restricted CD8+ T cells in the induction of a classical Ab-mediated disease, experimental autoimmune myasthenia gravis (EAMG), we immunized beta 2 microglobulin (beta 2-m) gene-disrupted (beta 2 m-/-) C57BL10 (B10) mice, deficient in class I gene expression and CD8+ cells, and heterozygous (beta 2-m+/-) B10 mice with normal expression of class I molecules and sufficient CD8+ cells with Torpedo acetylcholine receptor in CFA, and assessed them for clinical and immunopathologic manifestations of EAMG. Despite MHC class I and CD8+ cell deficiency, beta 2-m-/- mice developed EAMG. Moreover, the incidence of EAMG in the beta 2-m-/- mice was higher than that of beta 2-m+/- heterozygous mice with normal class I expression and frequency of CD8+ cells. The finding provided direct genetic evidence against a pathogenic effector role in C57BL10 mice for MHC class I molecule and class I-restricted CD8+ T cells in EAMG pathogenesis.
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PMID:Effect of MHC class I and CD8 cell deficiency on experimental autoimmune myasthenia gravis pathogenesis. 796 85

Islet transplantation can provide a therapeutic option for patients who suffer from type 1 diabetes mellitus, especially if current aggressive immunosuppression could be eliminated. In vitro immunomodulation has achieved this goal for islet allografts--however, strategies must be developed to prevent B cell lysis secondary to the chronic autoimmune process of diabetes. Previously, we have found that adjuvant therapy with CFA was effective in preventing the onset of diabetes and the recurrence of B cell lysis post-islet transplantation. In this study we evaluated the efficacy of BCG, a more clinically relevant immunoadjuvant, to prevent recurrent autoimmune damage to islets grafted into diabetic NOD mice. Highly purified islets were isolated from either 5-7-week-old prediabetic NOD mice or 5-8-week-old CBA/J mice using standard islet isolation techniques. Four hundred purified islets were transplanted into the kidney capsule of diabetic NOD recipients. A single dose of BCG was administered in recipients of syngeneic (gp 1) and allogeneic islets (gp 2). In gp 1, 8 of 10 BCG-treated syngeneic recipients remained normoglycemic for > 100 days posttransplant. In untreated recipients of syngeneic islets (gp 3) the graft failed at 19 days (n = 16) (P value, gp 1 vs. gp 3 < 0.001). In untreated allograft recipients, islet grafts functioned for 11 days (n = 8), which did not differ significantly (P = NS) from the BCG-treated allografts (gp 4) (14 days, n = 7). In 6 mice with long-term graft function, a second syngeneic graft implanted into the contralateral kidney maintained normoglycemia for 50 days following the removal of the first islet graft. Histological examination of the grafts from gp 1 mice showed granulated B cells with periinsular lymphocytes, while those of the control animals showed lytic B cells and marked lymphocytic infiltration. We conclude that adjuvant therapy with a single dose of BCG can prevent the recurrent autoimmune insulitis, but not allograft rejection in islets transplanted into NOD mice, and that a state of unresponsiveness is induced to allow acceptance of a second syngeneic graft. These data suggest that adjuvant therapy may be useful to sustain the function of transplanted islets in the type 1 diabetic.
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PMID:BCG immunotherapy prevents recurrence of diabetes in islet grafts transplanted into spontaneously diabetic NOD mice. 817 49


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