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)

The combined extracts obtained from three Chinese herb medicine, Kalopanax pictus, Pueraria thunbergiana and Rhus verniciflua, have been used as therapeutics for diabetes mellitus in Korea. In the present study, we have investigated their possible anti-inflammatory effects by comparing the potency of individual extracts with that of the combined extracts. An individual water extract prepared from Kalopanax pictus, Pueraria thunbergiana, and Rhus verniciflua was named K-1, P-1, and R-1, respectively. Simultaneously, we also prepared the combined extracts from above three plant materials by identical methods and named KPR-1. These four extracts were further fractionated into the EtOAc extracts, and these were designated as K-2, P-2, R-2, and KPR-2, respectively. These eight samples were subjected to the nitrite assays in LPS-induced macrophage 264.7 cells. KPR-2 exhibited the most pronounced effect on the inhibition of NO production among all the extracts. KPR-2 also significantly decreased PGE2, and TNF-alpha release. In addition, KPR-2 showed in vivo anti-inflammatory activity against acute paw edema induced by carrageenan in rats. When analgesic activity was measured by the acetic acid-induced abdominal constriction and hot plate test, KPR-2 showed a dose-dependent inhibition in animal models. These results suggested that the mixture extract and successive fractionation could lead to the better use of anti-inflammatory medicinal crude drugs.
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PMID:Anti-inflammatory and anti-nociceptive effects of the extract from Kalopanax pictus, Pueraria thunbergiana and Rhus verniciflua. 1526 79

Macrophages are potent regulators of both innate and adaptive immunity. They play a central role in the development of autoimmune diabetes and are among the first cells to appear in peri-islet infiltrates of NOD mice that spontaneously develop diabetes. Since efficient adhesion and migration are crucial for proper macrophage trafficking, we examined the migration and fibronectin (FN) adhesion capacity of NOD macrophages, as well as the regulation and expression of the FN receptors alpha4beta1 and alpha5beta1. When compared to macrophages from control strains, resident NOD macrophages showed a reduced ability to adhere to and migrate on FN, a delayed clearance following peritoneal inflammation, and substantially lower expression levels of the alpha4beta1 integrin alpha chain, CD49d. NOD bone marrow-derived macrophages were specifically defective in the LPS-induced increase in CD49d expression. Moreover, the mitogen-activated protein kinase extracellular signal-regulated kinase-1/2 negatively regulated macrophage CD49d expression and strongly suppressed its expression in NOD macrophages. The data presented herein indicate that the LPS-activated signaling cascade plays a critical role in CD49d expression of macrophages. Mature NOD macrophages are characterized by decreased CD49d expression and show defective CD49d-mediated adhesion to FN.
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PMID:Defective up-regulation of CD49d in final maturation of NOD mouse macrophages. 1551 11

Little is known about the pathogenic role of B cell dysfunction in T cell-mediated autoimmune disease. We previously reported that B cell hyper-responsiveness, resistance to apoptosis, and accumulation in islets occur during the onset of insulitis, but not in type 1 diabetes (T1D), in NOD mice. In this study we extended these studies to further determine how islet-infiltrated B cells contribute to this inflammatory insulitis. We demonstrate the presence of an increased percentage of B7-1(+) and a decreased percentage of B7-2(+) B cells in the spleen of autoimmune disease-prone NOD and nonobese diabetes-resistant mice compared with the spleen of nonautoimmune disease-prone C57BL/6 and BALB/c mice. An age-dependent differential expression of B7-1 and B7-2 was associated with the development of insulitis and CD4(+)CD25(+) T cell deficiency in autoimmune disease-prone mice. Whereas BCR and LPS stimulation increased B7-2 expression on B cells from autoimmune disease-prone and nonautoimmune disease-prone mice, LPS-induced B7-1 expression was higher on NOD than C57BL/6 B cells. Interestingly, increased expression of B7-1 and B7-2 was found on islet-infiltrated B cells, and this increase was associated with enhanced T cell costimulation. Islet-infiltrated B cells were shown to be a source of TNF-alpha production in islets. B7 blockade of BCR-stimulated NOD B cells by anti-B7-1 and anti-B7-2 mAbs during coadoptive transfer with diabetogenic T cells into NOD.scid mice protected these recipients from T1D. These results suggest that increased B7-1 and B7-2 expression on islet-infiltrated NOD B cells is associated with increased T cell costimulation and the development of inflammatory insulitis in NOD mice.
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PMID:Dysregulated B7-1 and B7-2 expression on nonobese diabetic mouse B cells is associated with increased T cell costimulation and the development of insulitis. 1563 86

Loss of tolerance is considered to be an early event that is essential for the development of autoimmune disease. In contrast to this expectation, autoimmune (type 1) diabetes develops in NOD mice that harbor an anti-insulin Ig transgene (125Tg), even though anti-insulin B cells are tolerant. Tolerance is maintained in a similar manner in both normal C57BL/6 and autoimmune NOD mice, as evidenced by B cell anergy to stimulation through their Ag receptor (anti-IgM), TLR4 (LPS), and CD40 (anti-CD40). Unlike B cells in other models of tolerance, anergic 125Tg B cells are not arrested in development, and they enter mature subsets of follicular and marginal zone B cells. In addition, 125Tg B cells remain competent to increase CD86 expression in response to both T cell-dependent (anti-CD40) and T cell-independent (anti-IgM or LPS) signals. Thus, for anti-insulin B cells, tolerance is characterized by defective B cell proliferation uncoupled from signals that promote maturation and costimulator function. In diabetes-prone NOD mice, anti-insulin B cells in this novel state of tolerance provide the essential B cell contribution required for autoimmune beta cell destruction. These findings suggest that the degree of functional impairment, rather than an overt breach of tolerance, is a critical feature that governs B cell contribution to T cell-mediated autoimmune disease.
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PMID:Uncoupling of anergy from developmental arrest in anti-insulin B cells supports the development of autoimmune diabetes. 1563 4

OGG-1 DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. It excises 7,8-dihydro-8-oxoguanine, which is formed by oxidative damage of guanine. We have investigated the role of OGG-1 in inflammation using three models of inflammation: endotoxic shock, diabetes, and contact hypersensitivity. We found that OGG-1(-/-) mice are resistant to endotoxin (lipopolysaccharide, LPS)-induced organ dysfunction, neutrophil infiltration and oxidative stress, when compared with the response seen in wild-type controls (OGG(+/+)). Furthermore, the deletion of the OGG-1 gene was associated with decreased serum cytokine and chemokine levels and prolonged survival after LPS treatment. Type I diabetes was induced by multiple low-dose streptozotocin treatment. OGG-1(-/-) mice were found to have significantly lower blood glucose levels and incidence of diabetes as compared with OGG-1(+/+) mice. Biochemical analysis of the pancreas showed that OGG-1(-/-) mice had greater insulin content, indicative of a greater beta-cell mass coupled with lower levels of the chemokine MIP-1alpha and Th1 cytokines IL-12 and TNF-alpha. Levels of protective Th2 cytokines, IL-4 and IL-10 were significantly higher in the pancreata of OGG-1(-/-) mice as compared with the levels measured in wild-type mice. In the contact hypersensitivity induced by oxazolone, the OGG-1(-/-) mice showed reduced neutrophil accumulation, chemokine, and Th1 and Th2 cytokine levels in the ear tissue. The current studies unveil a role for OGG-1 in the regulation of inflammation.
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PMID:Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation. 1567 45

1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] prevents autoimmune diabetes in nonobese diabetic (NOD) mice. A major target for 1,25(OH)(2)D(3) in the immune system is the dendritic cell (DC). Since important DC abnormalities have been described in NOD mice, we investigated the effects of 1,25(OH)(2)D(3) on the yield and phenotype of DCs generated from bone marrow of NOD mice compared to control congenic nonobese diabetes-resistant (NOR) mice. In both mouse strains, exposure of the bone marrow-derived cells to 1,25(OH)(2)D(3) increased the proportion of CD11c(+) DCs after culture. Surface expression of MHC II, CD86, and CD54 on NOR-derived DCs was decreased after 1,25(OH)(2)D(3) treatment, while CD40 remained unchanged. On NOD-derived DCs, 1,25(OH)(2)D(3) only inhibited the expression of MHC II and CD86. 1,25(OH)(2)D(3) inhibited IL-12 and IL-10 secretion after IFNgamma and LPS stimulation. In vitro treatment with 1,25(OH)(2)D(3) alters DC yield from bone marrow cultures and alters the phenotype of the cells in NOD as well as in NOR mice. NOD-derived DCs were more resistant to the 1,25(OH)(2)D(3) effects than were NOR-derived DCs.
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PMID:1,25-Dihydroxyvitamin D3 alters the profile of bone marrow-derived dendritic cells of NOD mice. 1569 15

Extracellular heat shock protein 60 (HSP60) has been considered a proinflammatory danger signal. Yet, HSP60 can also down-regulate experimental immune arthritis and diabetes models by specific inhibition of Th1-like responses. We now report that HSP60 in vitro differentially modulates the expression of Th1/Th2 transcription factors in human T cells: HSP60 down-regulates T-bet, NF-kappaB, and NFATp and up-regulates GATA-3, leading to decreased secretion of TNF-alpha and IFN-gamma and enhanced secretion of IL-10. These effects depended on TLR2 signaling and could not be attributed to LPS or to other contaminants. In BALB/c mice, HSP60 in vivo inhibited the clinical, histological, and serological manifestations of Con A-induced hepatitis associated with up-regulated T cell expression of suppressor of cytokine signaling 3 and GATA-3 and down-regulated T-bet expression. These results provide a molecular explanation for the effects of HSP60 treatment on T cell inflammation via innate regulation of the inflammatory response.
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PMID:Heat shock protein 60 inhibits Th1-mediated hepatitis model via innate regulation of Th1/Th2 transcription factors and cytokines. 1574 53

Chronic inflammation appears to play a critical role in type 2 diabetes and its complications. Here we tested the hypothesis that this inflammatory dysregulation affects the IL-1beta system and has functional consequences in the brain. Diabetic, db/db, and nondiabetic, db/+, mice were administered i.p. LPS, a potent cytokine inducer, at a dose of 100 microg/kg/mouse. db/db mouse innate immune-associated sickness behavior was 14.8, 33, 44.7, and 34% greater than that of db/+ mice at 2, 4, 8, and 12 h, respectively. When a fixed dose of LPS was used (5 microg/mouse), db/db mouse sickness was again enhanced 18.4, 22.2, and 14.5% at 4, 8, and 12 h as compared with db/+ mice. In diabetic mice, peritoneal macrophages produced more IL-1beta in response to LPS, and peritoneal levels of IL-1beta induced by LPS were increased. Importantly, IL-1R antagonist and type 2 IL-1 receptor (IL-1R2) failed to up-regulate in response to LPS in db/db mice. Finally, both peripheral and central administration of IL-1beta, itself, induced sickness in db/db mice that mimicked the effects of peripheral LPS and was significantly greater than that seen in db/+ mice. Taken together, these results indicate that IL-1beta-mediated innate immunity is augmented in db/db mice both at the periphery and in the brain, and the mechanism is due to diabetes-associated loss of IL-1beta counterregulation.
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PMID:IL-1beta-mediated innate immunity is amplified in the db/db mouse model of type 2 diabetes. 1581 29

The anti-diabetic effect of cytogenin was examined using streptozotocin-induced diabetes in mice. Cytogenin suppressed not only the increase of plasma glucose level but also the body weight reduction in diabetic mice. Histological examination of the pancreas taken from diabetic mice given cytogenin showed that cytogenin decreased the number of macrophages infiltrated into islet of pancreas. Further, cytogenin suppressed the nitric oxide generation by macrophages treated with lipopolysaccharide through decreasing of inducible nitric oxide synthase expression. Cytogenin suppressed interleukin-6 expression by macrophage treated with LPS, suggesting that the anti-diabetic activity of cytogenin might be partly attributed to the suppressive activity against nitric oxide generation.
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PMID:Effect of cytogenin, a novel immunomodulator, on streptozotocin-induced diabetes in mice. 1589 29

BB rats develop various organ-specific autoimmune diseases, e.g. autoimmune diabetes and thyroiditis and have proven important to dissect genetic factors that govern autoimmune disease development. The lymphopenia (lyp) gene (iddm2) is linked to autoimmune disease development and is a major genetic difference between diabetes-resistant (DR) and diabetes-prone (DP) BB rats. To study the effects of the lyp gene and other genes on dendritic cell (DC) differentiation from bone-marrow precursors, such differentiation was studied in BB-DP, BB-DR, Wistar and F344 control rats. DC of BB-DP rats showed a lower MHC class II expression as compared to BB-DR, Wistar and F344 rats. LPS-maturation did not restore this low MHC class II expression. DC of BB-DP rats also showed a poor capability to terminally differentiate into mature T cell stimulatory DC under the influence of LPS and produced significantly lower quantities of IL-10, yet these aberrancies were also found in BB-DR rats but did not occur in control rats. This study thus shows that various aberrancies exist in the differentiation of myeloid DC from bone-marrow precursors in the BB rat model of organ-specific autoimmunity. These aberrancies are multigenically determined and partly associated with iddm2 (lyp gene) and partly associated with other genes in the BB rat.
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PMID:Defects in differentiation of bone-marrow derived dendritic cells of the BB rat are partly associated with IDDM2 (the lyp gene) and partly associated with other genes in the BB rat background. 1592 63


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