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)

Alloxan diabetic BALB/C mice with high hyperglycaemia levels (larger than or equal to 600 mg/100 ml) when immunized either with T-dependent (SRCB) or T-independent (TNP-LPS) antigens show a significant decrease in the number of specific PFC when compared with normo-glycaemic controls. Moderate diabetes (greater than 350 mg/100 ml) does not affect the immune response and in some experiments a slight increase of anti-SRBC plaques was seen. In transfer experiments primed spleen cells of either diabetic or normal doners gave much better responses when transferred to normal rather than diabetic X-irradiated recipients. In Mishell-Dutton (MD) cultures anti-SRBC response of CBA spleen cells was moderately reduced only when the blood glucose level of cell donors exceeded 500 mg/100 ml. Glucose added to MD cultures of normal spleen cells diminished significantly the number of SFC when in concentrations exceeding 600 mg/100 ml. The data indicate that in diabetic animals B-lymphocyte function may be affected but give no clear-cut answer to whether this is also true for T-helper cells. Disabled lymphocytes, whatever population they represent, may partially recover when transferred into normo-insulinic milieu. It may be inferred that under conditions tested neither hyperglycaemia nor excess of corticosteroid accounted significantly for the impaired humoral responses in diabetic animals. These experiments imply, however, that in hypoinsulinaemia the lack of saturation of insulin receptors on the lymphocyte, and possibly also macrophage, membranes renders these cells functionally inactive presumably due to accumulation of cyclic AMP in the cell membrane.
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PMID:Impaired antibody responses in alloxan diabetic mice. 33 63

In the present study we searched for restriction fragment length polymorphisms (RFLP) in the human interleukin-1 beta (IL-1 beta) gene and for correlations to monocyte (Mo) function in non-related healthy donors and insulin-dependent diabetic patients. We demonstrated a diallelic polymorphism with the restriction enzyme TaqI consisting of fragments of 9.4 kb and 13.4 kb. No differences in allele or genotype frequencies of this RFLP were observed between randomly selected controls and randomly selected patients with insulin-dependent diabetes mellitus (IDDM). However, when analysing IDDM patients negative for HLA-DR3 and -DR4, our data demonstrate that the 13.4 kb allele is more frequent in this group compared to a matched control group. The functional impact of this RFLP was studied by analysing in vitro stimulated Mo IL-1 beta response. An IL-1 beta allele dosage effect on secretory capacity was observed after LPS-stimulation: 13.4/13.4 kb homozygous individuals secreted significantly more IL-1 beta than 9.4/13.4 kb heterozygous individuals, who secreted significantly more than 9.4/9.4 kb homozygous individuals. Analyses of supernatants from LPS-stimulated Mo cultures from individuals with each TaqI IL-1 beta genotype revealed no differences in the mouse thymocyte co-stimulatory assay when compared on a molar basis, indicating that the TaqI polymorphism gave rise only to quantitative differences in expression levels and probably not to a mutant IL-1 beta.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. 135 22

It has been shown earlier in an in-vitro model of inflammatory islet cell death that activated macrophages lyse islet cells via the release of nitric oxide. Here we report that cyclosporin A suppresses macrophage cytotoxicity. Control experiments showed that the immunosuppressive drug does not improve the defences of islet cells against nitric oxide but inhibits the release of nitric oxide from LPS-stimulated macrophages. This property of cyclosporin A may contribute to the preservation of beta cell function seen in cyclosporin A-treated patients with recent onset type I diabetes.
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PMID:Cyclosporin A protects pancreatic islet cells from nitric oxide-dependent macrophage cytotoxicity. 142 69

We have recently reported that chronic and systemic administration of tumor necrosis factor alpha (TNF) inhibits development of autoimmune diabetes in NOD mice and BB rats, animal models of insulin-dependent diabetes mellitus (IDDM). During these experiments, we unexpectedly found that in vivo production of TNF stimulated by a single injection of lipopolysaccharide was enhanced approximately 10 times in the long-term diabetic BB rats (P less than 0.0001), whose mean duration of diabetes with more than 16.8 mM (300 mg/dl) of nonfasting blood glucose level was 26.2 +/- 2.1 days, as compared to that in the rats of nondiabetes and in the rats at the onset of diabetes, whose mean duration of diabetes was 1.4 +/- 0.6 days. The long-term diabetic, but not short-term-diabetic, rats were also associated with increased levels of serum fructosamine/albumin (P less than 0.01) and triglyceride (P less than 0.01) and with a decreased level of serum albumin (P less than 0.01). The in vivo TNF productivity in the diabetic rats, including the short-term- and long-term-diabetic rats, was correlated positively with the level of fructosamine/albumin (P less than 0.05) and negatively with the level of serum albumin (P less than 0.05), but not with levels of blood glucose. None of these correlations were observed in nondiabetic rats. The increased LPS-induced serum TNF activity in the long-term diabetic state was observed not only in BB rats but also in NOD mice and GK rats, a model of non-IDDM, irrespective of sexes and ages, indicating that the enhancement of in vivo TNF production was a result of long-term diabetes. These findings indicate that some factor(s) associated with the long-term-diabetic state may prime macrophages in vivo to produce TNF. Further study is needed to reveal a mechanism of the enhanced TNF production and its possible relevance to various abnormalities associated with the chronic hyperglycemic state.
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PMID:Increased in vivo production of tumor necrosis factor after development of diabetes in nontreated, long-term diabetic BB rats. 154 Oct 51

With the aim of clarifying the mechanism of the suppressive action of BCG against insulitis and overt diabetes in NOD mice, we studied the effects of BCG on spleen cell populations and on the in vitro immune responses of spleen cells. The spleen cells of BCG-vaccinated mice showed much lower responsiveness to various mitogens such as Con A, PHA, PWM, and LPS than those of saline-treated mice. Low responsiveness to alloantigens was also observed. Flow cytometric analysis of the spleen cells revealed that Mac-1+ and Mac-2+ cells had increased while T and B cells had decreased in the BCG-vaccinated mice compared with the saline-treated mice at the time when the maximum level of inhibition of mitogen responses of BCG-vaccinated mice was observed. This suggests that the decreased in vitro immune response was due to the increase in macrophages which suppress lymphocyte functions. Support for this interpretation comes from the following two findings: (1) the restoration of mitogen responses of spleen cells when macrophages were eliminated by plastic adhesion or FACS sorting and (2) resuppression of PHA and Con A responses of plastic-nonadherent spleen cells by addition of adherent cells or flow cytometrically sorted Mac-1+ cells obtained from BCG-vaccinated mice. These results indicate the generation of suppressor macrophages after BCG vaccination and suggest that these macrophages prevent the autoimmune pathogenesis leading to diabetes in NOD mice.
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PMID:Possible mechanism of the preventive effect of BCG against diabetes mellitus in NOD mouse. I. Generation of suppressor macrophages in spleen cells of BCG-vaccinated mice. 183 72

Rat neutrophil chemotactic responses to N-formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene (LT) B4, and lipopolysaccharide-activated serum (LPS-AS) were quantitatively assessed using the micropore filter system. Cells were suspended in either normal or diabetic rat serum for testing. Diabetic donor serum did not affect migration of neutrophils in a concentration gradient of the synthetic chemotactic agents. In contrast, the migratory responses to LPS-AS were significantly less than normal in this circumstance. Summation of effects was observed when FMLP and LPS-AS, or LTB4 and LPS-AS were simultaneously added to the test chamber, with cells suspended in normal serum. Suspended in diabetic rat serum neutrophils responded normally to the synthetic chemoattractants but the response to the activated serum was blocked. Cells previously incubated in the presence of diabetic donor serum then transferred to a culture medium for testing, presented reduced migratory responses to LPS-AS. Supramaximal, inhibitory concentrations of FMLP and LTB4, did not influence the response of neutrophils to LPS-AS. In vivo, suppression of cellular emigration to an inflamed area was observed from the early stages of the diabetic state. The inhibitory activity of chemotaxis in diabetes mellitus was previously reported to be associated with a protein factor in plasma of the animals. It is suggested that the inhibitory factor of chemotaxis in diabetes mellitus interacts with neutrophil receptors for complement-derived chemoattractants to induce blockade of cell-oriented locomotion either in vitro or in vivo.
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PMID:Inhibition of leukocyte chemotaxis by serum factor in diabetes mellitus: selective depression of cell responses mediated by complement-derived chemoattractants. 216 2

IgG antibody levels to lipoteichoic acid (LTA), prepared from Streptococcus mutans cells, were determined by enzyme-linked immunosorbent assay in serum samples from 149 subjects. An extract from Bacteroides gingivalis and lipopolysaccharide from Escherichia coli 055:B5 served as control antigens. The reference group comprised 28 systemically and periodontally healthy adults. The main test groups were: 52 persons with gingivitis only, and 69 patients with periodontitis. Within those groups, 37 patients had insulin-dependent diabetes mellitus, another 20 patients were prospective or renal transplant recipients. The periodontitis patient group showed significantly (p less than 0.05) higher mean antibody value and higher frequency of extreme antibody responses to both LTA and B. gingivalis than the gingivitis group. LPS did not discriminate between the groups. Multiple regression analysis with gingivitis scores as the dependent variable selected plaque scores, anti-LTA antibody values and general health status as significant (p less than 0.05) regressors. The variance in radiographical alveolar bone loss was significantly (p less than 0.05) explained by age and by antibody values to B. gingivalis and to LTA. The patients with extreme immunological responsiveness to LTA or to B. gingivalis had about twice as much alveolar bone loss as those with normal serological reactivity. The results support the contention that LTA modulates the progression of periodontitis in humans.
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PMID:Serum IgG antibodies reactive with lipoteichoic acid in adult patients with periodontitis. 277 86

We previously reported that administration of a streptococcal preparation (OK-432) inhibited insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and BB rats as animals models of insulin-dependent diabetes mellitus. In this study, we screened various cytokines that could be induced by OK-432 in vivo, for their preventive effect against diabetes in NOD mice. Among recombinant mouse IFN gamma, human IL1 alpha, human IL2, mouse granulocyte-macrophage colony-stimulating factor and human TNF alpha, only human TNF alpha suppressed insulitis and significantly (P less than 0.001) inhibited development of diabetes. NOD mice were the lowest producers of the mRNA of TNF and serum TNF on stimulation with OK-432 or with IFN gamma plus LPS, compared with C57BL/6, C3H/He, and Balb/c mice. The results imply a role for low productivity of TNF in the pathogenesis of autoimmune diabetes in NOD mice.
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PMID:Recombinant human tumor necrosis factor alpha suppresses autoimmune diabetes in nonobese diabetic mice. 279 65

Nonobese diabetic (NOD) is an inbred mouse strain susceptible to development of T cell-mediated autoimmune diabetes. The strain is characterized by high percentages of T lymphocytes in lymphoid organs. The syngeneic mixed lymphocyte reaction (SMLR), a T cell response to self MHC class II Ag, is reportedly involved in the generation of a number of immunoregulatory cells, including suppressor inducers. A severely depressed SMLR characteristic of certain other autoimmune strains was found in NOD but not in nonautoimmune SWR/Bm mice. Moreover, IL-2 produced by NOD T cells at day 6 in an SMLR was at least one hundredfold reduced compared with SWR, and NOD T cells harvested from an SMLR at day 6 were functionally defective when tested for ability to induce suppression of an allogeneic MLR. However, functionally competent suppressor T cells were generated in NOD splenic leukocyte cultures in response to Con A, and IL-2 release from these was equivalent to that released by Con A-stimulated SWR splenocytes. A deficiency in cytokine release was not limited to IL-2, because peritoneal exudate cells from NOD exhibited a greatly diminished sensitivity to LPS-stimulated IL-1 release in comparison to SWR mice. IL-2 supplementation both in vitro and in vivo restored the ability of NOD T cells to respond in a SMLR, with production of cells capable of inducing suppression. Like SMLR-activated T cells from untreated SWR controls, SMLR blasts from IL-2-treated NOD mice were enriched for the L3T4 phenotype. IL-1 supplementation in vitro resulted in partial restoration of T suppressor activation in a SMLR. The depressed SMLR exhibited by NOD mice was apparently a stimulator cell dysfunction, because NOD stimulator cells failed to activate T cells from (SWR x NOD)F1 mice, whereas stimulators from SWR or F1 mice were capable of doing so. Collectively, these results suggest a defect in suppressor cell activation rather than an absence of this immunoregulatory cell population.
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PMID:Defective activation of T suppressor cell function in nonobese diabetic mice. Potential relation to cytokine deficiencies. 289 95

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


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