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)

Reduced interleukin-10 (IL-10) production is associated with type 2 diabetes in elderly individuals. Antiviral therapy (ARV)-induced immune modulation results in diminished IL-10 production, and diabetes can be observed in ARV-treated human immunodeficiency virus (HIV)-infected individuals. We analyzed, in a cross-sectional pilot study, HIV-antigen-stimulated IL-10 and tumor necrosis factor alpha (TNFalpha) production, and intracellular concentration (ICC), as well as B7-H1 expression, a marker preferentially presented by IL-10-producing cells, in 20 ARV-treated individuals in whom diabetes did (n=10; diabetes mellitus, DM) or did not (n=10; controls) develop. Pre-ARV glucose, cholesterol, and triglycerides levels, duration of HIV infection and of therapy, exposure to protease inhibitors (PI), HIV plasma viremia, CD4 counts, and nadir were similar in DM and control patients. Results showed that: (1) IL-10 production was lower; (2) IL-10 ICC was reduced; (3) B7-H1-expressing CD19(+) cells were diminished; and (4) TNFalpha production and ICC by CD4(+) T cells was augmented in DM patients. Development of diabetes in HIV infected, ARV-treated individuals could be a response to therapy. Similar to what is observed in elderly individuals, low IL-10 production is associated with diabetes in antiviral-treated HIV infection. Further studies will be necessary to clarify whether low IL-10 is a risk factor for, or a consequence of, diabetes.
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PMID:Low interleukin-10 production is associated with diabetes in HIV-infected patients undergoing antiviral therapy. 1643 43

We examined the association between interleukin-10 (IL-10), adiponectin levels and inflammatory markers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP). Furthermore, the association of these anti-/pro-inflammatory cytokine levels with the metabolic syndrome was investigated. The study subjects were composed of 312 Korean individuals without diabetes. Serum adiponectin level was associated with hsCRP (r=-0.21, P<0.001), IL-6 (r=-0.13, P<0.05) and IL-10 (r=-0.22, P<0.001) levels. Subjects without the metabolic syndrome showed higher adiponectin (17.03 microg/ml versus 13.85 microg/ml, P<0.001) and IL-10 (4.74 pg/ml versus 4.34 pg/ml, P=0.014) levels, and lower serum hsCRP (0.38 microg/ml versus 0.66 microg/ml, P=0.001) and IL-6 (0.94 pg/ml versus 1.32 pg/ml, P=0.009) levels compared to those with the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome was associated with sex, age, waist circumference, systolic blood pressure, HDL cholesterol, triglyceride, fasting blood glucose and interleukin-10. Furthermore, serum adiponectin levels are associated with serum hsCRP, IL-6 and IL-10 levels. These results suggest that adiponectin might be associated with the metabolic syndrome through regulation of pro-/anti-inflammatory cytokines.
Diabetes Res Clin Pract 2007 Feb
PMID:Serum adiponectin, interleukin-10 levels and inflammatory markers in the metabolic syndrome. 1687 12

Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet beta cell destruction can be manipulated by the administration of Th(2) cytokines. In this article, the effect of interleukin-10 (IL-10) gene delivery was evaluated in vitro and in vivo with a novel IL-10 plasmid, pSI-IL-10-NFkappaB. In pSI-IL-10-NFkappaB, the expression of the IL-10 gene was driven by the SV40 promotor/enhancer. The nuclear factor kappaB (NFkappaB) binding sites were also introduced to facilitate nuclear transport of the plasmid in the cell. In vitro transfection assay with pSI-IL-10-NFkappaB showed a similar expression level of IL-10 to the plasmid without NFkappaB binding sites (pSI-IL-10). pSI-IL-10-NFkappaB and pSI-IL-10 were intravenously injected into 5-week-old nonobese diabetic (NOD) mice using polyethylenimine (PEI) as a gene carrier. Both groups had persistent gene expression, longer than 5 weeks, and secreted the similarly high IL-10 serum levels. Interestingly, the degree of insulitis in the pSI-IL-10-NFkappaB group was improved over the pSI-IL-10 group, PEI-only group, and noninjected controls. The serum glucose levels showed that single injection of pSI-IL-10-NFkappaB prevented the development of diabetes in 100% of the pSI-IL-10-NFkappaB-injected animals (5/5), while that of pSI-IL-10 prevented diabetes in 40% of the treated animals (2/5). These results suggest that pSI-IL-10-NFkappaB with PEI can effectively reduce the incidence of insulitis and type 1 diabetes in NOD mice.
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PMID:Interleukin-10 plasmid construction and delivery for the prevention of type 1 diabetes. 1713 May 72

Islet transplantation is an attractive approach for treating type-1 diabetes, but there is a massive loss of transplanted islets. It is currently only possible to estimate islet mass indirectly, through measurement of circulating C-peptide and insulin levels. This type of estimation, however, is not sufficiently sensitive or reproducible for follow-up of individuals who have undergone islet transplantation. Here we show that islet graft survival could be assessed for 1 month in diabetic NOD mice using 9-(4-[(18)F]-fluoro-3-hydroxymethylbutyl)guanine ([(18)F]FHBG)-positron emission tomography (PET) technology, the PET signal reflecting insulin secretory capacity of transplanted islets. Expression of the gene encoding viral interleukin-10 (vIL-10), was measurable in real time with PET scanning. Additionally, we addressed the clinical potential of this approach by visualizing transplanted islets in the liver, the preferred clinical transplantation site. We conclude that quantitative in vivo PET imaging is a valid method for facilitating the development of protocols for prolonging islet survival, with the potential for tracking human transplants.
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PMID:Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. 1714 77

Chronic low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease and type 2 diabetes. Regular exercise offers protection against all-cause mortality, primarily by protection against atherosclerosis and insulin resistance and there is evidence that physical training is effective as a treatment in patients with chronic heart diseases and type 2 diabetes. Regular exercise induces anti-inflammatory actions. During exercise, IL-6 (interleukin-6) is produced by muscle fibres. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra (interleukin-1 receptor antagonist) and IL-10 (interleukin-10) and inhibits the production of the pro-inflammatory cytokine TNF-alpha (tumour necrosis factor-alpha). In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. It is suggested that regular exercise induces suppression of TNF-alpha and thereby offers protection against TNF-alpha-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine, that is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body. Myokines may be involved in mediating the beneficial health effects against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.
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PMID:The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. 1714 83

In vivo induction of beta-cell apoptosis has been demonstrated to be effective in preventing type 1 diabetes in NOD mice. Based on the notion that steady-state cell apoptosis is associated with self-tolerance and the need for developing a more practical approach using apoptotic beta-cells to prevent type 1 diabetes, the current study was designed to investigate apoptotic beta-cells induced ex vivo in preventing type 1 diabetes. The NIT-1 cell line serves as a source of beta-cells. Apoptotic NIT-1 cells were prepared by ultraviolet B (UVB) irradiation. Three weekly transfusions of UVB-irradiated NIT-1 cells (1 x 10(5)/mouse) or PBS were used to determine whether transfusions of UVB-irradiated NIT-1 cells induce immune tolerance to beta-cell antigens in vivo and prevent type 1 diabetes. The suppression of anti-beta-cell antibodies, polarization of T-helper (Th) cells, and induction of regulatory T-cells by UVB-irradiated NIT-1 cell treatment were investigated. The transfusions of apoptotic NIT-1 cells suppress anti-beta-cell antibody development and induce Th2 responses and interleukin-10-producing regulatory type 1 cells. Importantly, this treatment significantly delays and prevents the onset of diabetes when 10-week-old NOD mice are treated. Adoptive transfer of splenocytes from UVB-irradiated NIT-1 cell-treated mice prevents diabetes caused by simultaneously injected diabetogenic splenocytes in NOD-Rag(-/-) mice. Moreover, the proliferation of adoptively transferred carboxyfluorescein diacetate succinimidyl ester-labeled beta-cell antigen-specific T-cell receptor-transgenic T-cells in UVB-irradiated NIT-1-cell treated mice is markedly suppressed. The transfusion of apoptotic beta-cells effectively protects against type 1 diabetes in NOD mice by inducing immune tolerance to beta-cell antigens. This approach has great potential for immune intervention for human type 1 diabetes.
Diabetes 2007 Aug
PMID:Transfusion of apoptotic beta-cells induces immune tolerance to beta-cell antigens and prevents type 1 diabetes in NOD mice. 1749 35

Independent of the association of obesity with dyslipidemia, hypertension, and increased propensity for diabetes, fatness per se is increasingly recognized as a cardiovascular offender. That adipose tissue releases a wide range of adipokines, growth factors, enzymes, and enzyme substrates linked to vascular injury provides a plausible explanation for the role of fat in vascular disease: tumor necrosis factor-alpha, leptin, resistin, interleukin-1, -6, -8, and -18, serum amyloid A, monocyte chemoattractant protein I, macrophage inhibitory factor, aortic carboxypeptidase, hepa-rin-binding epidermal growth factor-like growth factor, vascular endothelial growth factor, transforming growth factor beta, angiotensinogen, cathepsin S, estradiol, cortisol, mineralocorticoid releasing factor, and calcitonin peptides are probable fat-derived prothrombotic, proinflammatory, and proatherosclerotic agents acting in a paracrine and/or endocrine manner. Other adipocyte products such as adiponectin, transforming growth factor beta, and interleukin-10 exert some antiatherogenic effects. The following is a short overview of how adipose tissue products affect the vasculature.
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PMID:Fat cell-derived modulators of vascular cell pathophysiology: the list keeps growing. 1767 16

Type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, such as glutamic acid decarboxylase 65 (GAD65), for which islet transplantation is a promising therapy. Therefore, the generation of tolerance aiming at both alloantigen and GAD65 will help therapeutic intervention greatly in T1D. In this study, we tested the effect of programmed death-1 ligands (PD-L1)-transfected dendritic cells (DC) loaded with GAD65 on the alloresponse and GAD65-reactive lymphocyte response. The DC2.4 cell line was transfected with PD-L1 and co-cultured with GAD65. BALB-c mice were primed, respectively, by intraperitoneal injection with GAD65, PD-L1-transfected- or non-transfected DC (PD-L1/DC or DC), and PD-L1-transfected- or non-transfected DC loaded with GAD65 (PD-L1/DC/GAD65 or DC/GAD65). Splenocytes of treated mice were isolated and restimulated in vitro with GAD65 or the various DC populations above being used as stimulators, respectively. In the mixed lymphocyte reaction, DC/GAD65 were able to stimulate both allogeneic and GAD65-reactive lymphocytes. However, PD-L1/DC/GAD65 were poorer than DC/GAD65 at activating the GAD65-reactive lymphocyte response. Further, although PD-L1/DC could inhibit the alloresponse, PD-L1/DC/GAD65 were more effective at down-regulating the GAD65-reactive lymphocyte response. More importantly, PD-L1/DC/GAD65-primed lymphocytes exhibited the weakest proliferation when again restimulated in vitro by PD-L1/DC/GAD65. Additionally, PD-L1/DC/GAD65 down-regulated interferon-gamma and up-regulated interleukin-10 production by activated lymphocytes. Therefore, combined stimulation in vivo and in vitro by PD-L1/DC/GAD65 could inhibit both the alloresponse and the GAD65-reactive lymphocyte response, which may contribute to controlling diabetes and islet transplant rejection.
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PMID:Programmed death-1 ligands-transfected dendritic cells loaded with glutamic acid decarboxylase 65 (GAD65) inhibit both the alloresponse and the GAD65-reactive lymphocyte response. 1800 63

The application of anti-CD3 F(ab')(2) monoclonal antibodies has recently been expanded to treat established autoimmune diseases, including type 1 diabetes. However, the mechanism underlying their effect remains largely unclear. We report that short-phase administration of anti-CD3 F(ab')(2) antibodies efficiently allowed 80% of new-onset, nonobese diabetic (NOD) mice to significantly regain both normoglycemia and pancreatic beta cell-specific autoantigen (ie, glutamic acid decarboxylase and insulin) tolerance, with both effects lasting more than 40 weeks. The responsible mechanism appears to involve the induction and maintenance of a population of immunoregulatory CD1d-restricted natural killer T (NKT) cells, which were marked by an enhanced Th2 response and secretion of elevated levels of interleukin-10. In vivo neutralization of interleukin-4 and/or interleukin-10 bioactivity abrogated this anti-CD3-mediated effect. Importantly, when the cotransfer of NKT cells from the livers of anti-CD3-treated mice and splenocytes from untreated, acutely diabetic NOD mice was performed in NOD-severe combined immunodeficient mice, the NKT cells were sufficient to either delay or prevent the onset of diabetes compared with controls where only splenocytes were introduced. These data suggest that CD1d-restricted NKT cells may play a critical role in anti-CD3 antibody-induced diabetes remission and the restoration of immune tolerance.
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PMID:Induction of active tolerance and involvement of CD1d-restricted natural killer T cells in anti-CD3 F(ab')2 treatment-reversed new-onset diabetes in nonobese diabetic mice. 1834 26

Recent insight into the balance of self-tolerance and auto-aggression has raised interest in using human regulatory T (Treg) cells for adoptive immunotherapy of unlimited autoimmune diseases including type-1 diabetes, rhematoid arthritis and multiple sclerosis. The therapeutic use of Treg cells, however, is so far hampered by the inefficiency of current protocols in making them accessible for genetic manipulations. We report here that TCR/CD3 stimulation that is accompanied by extensive CD28 costimulation makes human Treg cells susceptible to retroviral gene transfer ex vivo while preserving their properties in vitro and in vivo. To show the power of genetic manipulation of human Treg cells, we engineered 'designer Treg cells' by retroviral expression of a chimeric immunoreceptor with defined specificity, which activates Treg cells in a ligand-dependent manner to proliferate, to secrete high amounts of interleukin-10 and to repress an ongoing cytolytic T-cell response in vivo. The procedure in genetically modifying human Treg cells ex vivo will open a panel of applications for their use in the adoptive therapy of deregulated immune responses.
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PMID:Redirecting human CD4+CD25+ regulatory T cells from the peripheral blood with pre-defined target specificity. 1955 34


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