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

Patients with diabetes mellitus (DM) show an increased susceptibility to bacterial infections due to the presence of neutrophil dysfunction. Susceptibility to tuberculosis has also been reported in such patients, however, the reason remains unclear. This study measured the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) by the peripheral monocytes of patients diagnosed with pulmonary tuberculosis accompanied by DM (TB+DM) and patients without DM complications (TB) using age-matched, healthy control subjects for comparison. Also examined was the relationship between cytokine production and DM control. The results were as follows: (1) The production of IL-1 beta, TNF alpha and IL-6 in TB patients was significantly higher than that observed in the healthy control subjects. (2) The production of IL-1 beta, TNF alpha and IL-6 in TB+DM patients was significantly lower than that observed in the TB patients. (3) The production of IL-1 beta and TNF alpha in TB+DM patients with poor control was significantly lower than that observed in the patients with good control. (4) The TNF alpha production had a significant inverse correlation to HbA1c in the TB+DM patients. This study demonstrated that the production of cytokines is impaired in TB+DM patients and suggests a close correlation between tuberculosis immunity and DM.
 ...
PMID:[Case study of interleukin-1 beta, tumor necrosis factor alpha and interleukin-6 production peripheral blood monocytes in patients with diabetes mellitus complicated by pulmonary tuberculosis]. 129 80

It has been proposed that certain cytokines secreted by islet-infiltrating leukocytes may be involved in the pathogenesis of insulin-dependent diabetes mellitus by participation in beta-cell destruction. In the present study, the impact of various cytokines on replication and long-term insulin secretion by pancreatic beta-cells was investigated. To this end, fetal rat pancreatic islets containing a high fraction of beta-cells were exposed in culture for 1-3 days to interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interferon-alpha (IFN-alpha), and interleukin-6 (IL-6) at different concentrations. It was found that IL-1 beta markedly decreased beta-cell DNA synthesis during the first day of exposure, an effect that vanished after 2 days and was turned into a potent and dose-dependent stimulation by 3 days of exposure. At this latter time point, IL-1 beta also amplified the mitogenicity of growth hormone (GH) and 16.7 mM glucose. In contrast, basal as well as glucose- and GH-stimulated insulin secretion was consistently suppressed by IL-1 beta from days 1-3. IL-1 beta also lowered the islet adenosine 3',5'-cyclic monophosphate (cAMP) content at all time points studied. However, addition of the stimulatory cAMP analogue Sp-diastereomer of adenosine 3',5'-cyclic monophosphothioate or pertussis toxin, which themselves enhanced DNA synthesis and insulin secretion, failed to prevent the inhibitory actions of IL-1 beta on these parameters, making it unlikely that a decrease in cAMP is an important event in transduction of the inhibitory effects of the cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Differential effects of cytokines on long-term mitogenic and secretory responses of fetal rat pancreatic beta-cells. 132 36

Insulin-dependent diabetes mellitus is an autoimmune phenomenon in humans. At onset, the diabetic pancreas shows a well-characterized insulitis. The inflammatory cells are specifically directed toward beta cells of the pancreatic islets. Several hypotheses link genetic susceptibility for diabetes to immunologic mechanisms. The cytokines interferon gamma and interleukin-6 have essential roles in the progressive destruction of beta cells. Studies with experimental models may improve definition of the pathogenesis of insulin-dependent diabetes mellitus. Combining genetic studies that detect susceptibility to insulin-dependent diabetes mellitus with future therapies aimed at interrupting cytokine production or cytokine receptor expression may lead to prevention of insulin-dependent diabetes mellitus.
 ...
PMID:Cytokines and the pathogenesis of insulin-dependent diabetes mellitus. 142 73

A panel of somatic cell hybrid cell lines containing different parts of human chromosome 20 and fluorescence in situ hybridization have been used to physically localize markers to human chromosome 20. Through these complementary approaches and genetic linkage analysis, D20S16, which is closely linked to the maturity onset diabetes of the young (MODY) locus, was mapped to band 20q12 --> q13.1. The gene for growth hormone-releasing factor (GHRF) was physically mapped and reassigned to 20q11, suggesting that GHRF plays no direct role in MODY. In addition, the genes for the chromosome 20-linked glycogen phosphorylase (GYPB) and the bone morphogenetic protein (BMP2A) have been assigned to chromosome 20p, and the interleukin-6-dependent DNA-binding protein (TCF5) has been assigned to 20q12 --> q13 by hybridization to genomic DNA from the panel of somatic cell hybrid cell lines. These approaches are useful for rapid localization of candidate genes for MODY and other DNA markers mapped to chromosome 20.
 ...
PMID:Physical localization of chromosome 20 markers using somatic cell hybrid cell lines and fluorescence in situ hybridization. 142 75

Viral infection has been suggested to play a triggering role in the pancreatic beta cell destruction which occurs in insulin-dependent diabetes (IDDM). However, the underlying mechanism of this phenomenon is unknown. In this study a human insulinoma cell line has been infected with measles, mumps and rubella viruses since a temporal association is reported between the clinical onset of IDDM and diseases caused by these viruses. The infection with measles and mumps viruses induced the release of interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cell line as assessed by a bioassay and up-regulated the expression of human leucocyte antigen (HLA) class I and class II antigens as evaluated by cytofluorimetric analysis. Stimulation with rubella virus induced the release of IL-6 only and had no effect on HLA antigen expression. These data show for the first time that IL-1 and IL-6 secretion by an insulinoma cell line may occur after viral infection and suggest that cytokine release and increased expression of HLA molecules by beta cells may act to induce the immune response towards beta cells in IDDM.
 ...
PMID:Viral infection induces cytokine release by beta islet cells. 159 39

It has been proposed that certain cytokines secreted by islet-infiltrating leukocytes may be involved in the pathogenesis of insulin-dependent diabetes mellitus. Since the cytotoxic actions by the cytokines may reflect interactions with islet cell types other than the beta-cell, in this work I have investigated the effects of different combinations of various cytokines on the proliferation and hormone content and secretion by a pure insulin-producing cell population, i.e., the clonal rat insulinoma cell line RINm5F. For this purpose RINm5F cells were exposed in culture for 1-2 days to interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and interferon alpha (IFN-alpha) at different concentrations. It was found that IL-1 beta markedly decreased the cellular content of insulin and secretion of the hormone into the culture medium, while causing a very slight inhibition of RINm5F cell proliferation. On the other hand, IFN-gamma and IFN-alpha both elicited marked decreases in proliferation and insulin content and secretion by the insulinoma cells. IL-6 and TNF-alpha were found not to affect these parameters. No additive or synergistic effects were observed when the cytokines were added in various combinations. There was no protection against the cytotoxicity of IL-1 beta, IFN-gamma or IFN-alpha by pre-treatment with pertussis toxin. From these findings it is concluded that the cytokines IL-1 beta, IFN-gamma and IFN-alpha act in a non-synergistic fashion in suppressing RINm5F cell proliferation and hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cytokines inhibit proliferation and insulin secretion by clonal rat insulinoma cells (RINm5F) non-synergistically and in a pertussis toxin-insensitive manner. 195 44

Evidence from epidemiological and histopathologic studies in humans with autoimmune type 1 (insulin-dependent) diabetes suggests that beta-cell destruction within the islets of Langerhans progresses through a number of stages. In this review we draw on recent experimental evidence in an attempt to define the molecular pathology of these stages. Stage 1 is postulated to be initiated by modification of the beta cell by virus, chemical or other factors, leading to the production of interferon-alpha, hyperexpression of major histocompatibility complex (MHC) class I molecules and induction of MHC class II molecules. Experiments in transgenic mice suggest that overexpression of MHC molecules is in itself detrimental to beta-cell function. Shedding of antigen(s) from dying beta cells in combination with hyperexpression of MHC molecules may be a powerful immunogenic stimulus. Stage 2 commences with infiltration of the islets by immuno-inflammatory cells (termed insulitis). It is proposed that production of cytokines from the infiltrating cells induces "phenotypic switching" in beta cells, with further upregulation of MHC molecules and the induction of intracellular adhesion molecule-1 expression and interleukin-6 production. Together, these properties are seen as a prerequisite for the presentation of autoantigen by beta cells to adherent T lymphocytes and autoimmune activation. The final stage encompasses autoimmune-mediated destruction of the beta cells by the targeted delivery of cytotoxic cytokines and other mediators.
 ...
PMID:Molecular pathology of type 1 diabetes. 223 44

Recently it has been postulated that interleukin-1 (IL-1) locally released by infiltrating mononuclear cells may destroy the pancreatic B cells during the development of insulin-dependent diabetes mellitus. Since IL-1 is a potent inducer of interleukin-6 (IL-6) in various cells, it is conceivable that IL-6 is a second mediator of the IL-1 action. In the present study the effects of IL-6 alone or in combination with IL-1 were studied on pancreatic islet function in vitro after tissue culture and compared with the effects observed after exposure to IL-1 only. Rat pancreatic islets were cultured in medium RPMI 1640 + 10% calf serum with or without the addition of human recombinant IL-6 (500-5000 pg/ml) for 48 h. The medium insulin accumulation was increased by 40-50% after culture with 500-2000 pg/ml IL-6, but was similar to the controls at 5000 pg/ml. When islets were cultured for 18 h only, also 5000 pg/ml IL-6 stimulated the medium insulin accumulation. IL-6 did not affect the islet insulin content and the rates of islet (pro)insulin and total protein biosynthesis. It inconsistently decreased the islet DNA content. In short-term experiments after 48-h culture with IL-6, there was a dose-dependent inhibition of the glucose-stimulated insulin release. On the other hand, islets cultured with IL-6 (5000 pg/ml) exhibited an elevated glucose oxidation and oxygen uptake, but a lower ATP content at 16.7 mM glucose and an unaffected glucose utilization and glutamine oxidation compared to the controls. This raises the possibility that IL-6 had induced a condition with an increased energy expenditure, resulting in an enhanced mitochondrial metabolism of glucose. Islets cultured with human recombinant IL-1 beta (25 units/ml) showed a strong inhibition of the insulin accumulation in the culture medium and of glucose-stimulated insulin release and a marked decrease in the islet DNA and insulin content. A combination of IL-1 (25 U/ml) + IL-6 (1000 pg/ml) did not alter the inhibitory action of IL-1 alone. The present findings thus show that IL-6 induces a dissociation between insulin secretion and glucose oxidation in islets in vitro. This has not been observed in islets exposed to IL-1, which suggests that IL-6 does not solely mediate the inhibitory effects of IL-1 on islet function.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-6 affects insulin secretion and glucose metabolism of rat pancreatic islets in vitro. 240 46

Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded polyribonucleotide that elicits immune responses analogous to those observed during viral infection. It is also known to modulate the expression of certain autoimmune disorders including diabetes mellitus in the BB rat and NOD mouse. The mechanism underlying these immunomodulatory effects is not known, but it could involve activation of vascular endothelium. We now report that parenteral poly I:C induces rat pancreatic endothelium to hyperexpress intercellular adhesion molecule 1 (CD54). This is accompanied by a perivascular recruitment of mononuclear cells to the exocrine pancreas. Corollary in vitro studies demonstrated that poly I:C is a potent activator of both rat and human endothelial cells in culture. It upregulates endothelial expression of several leukocyte adhesion molecules, stimulates the release of interleukin-6 and interleukin-8, and antagonizes interferon-gamma induction of major histocompatibility complex class II expression. We conclude that poly I:C activates endothelial cells to express surface molecules and cytokines in a pattern classically associated with leukocyte recruitment. These effects may in part contribute to the immunomodulatory effects of poly I:C in animal models of autoimmunity.
 ...
PMID:Polyinosinic:polycytidylic acid is a potent activator of endothelial cells. 751 92

To clarify the mechanism that causes elevation of plasma fibrinogen levels in diabetes, we examined the effect of high concentration of glucose and/or advanced glycosylation end products (AGEs) on the production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by human monocytes. Monocytes isolated from nine healthy volunteers were incubated with glucose, glucose with mannitol, or glucose with AGE-BSA for 24 or 48 h, respectively. IL-6 and TNF-alpha levels of culture supernatants were measured by ELISA methods. IL-6 and TNF-alpha levels of culture supernatants incubated with 22 mM or 33 mM glucose showed considerable increase over basal levels incubated with 11 mM glucose, whereas those levels incubated with high concentration of mannitol showed no increase. These two cytokine levels of culture supernatants, especially IL-6 level, showed synergistic elevation with AGE-BSA concentration. Our serial observation with treatment for lowering glucose levels showed that the diabetics with decreasing plasma fibrinogen levels also showed decrease in plasma IL-6 levels. In this study, we revealed the effect of glucose and AGEs on the production of IL-6 or TNF-alpha by human monocytes. These results suggest that hyperglycemia and AGEs will cause disregulated production of IL-6 and hyperfibrinogenemia in diabetics.
 ...
PMID:The effect of glucose and advanced glycosylation end products on IL-6 production by human monocytes. 769 4


1 2 3 4 5 6 7 8 9 10 Next >>