Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In most studies the activity of suppressor T cells and the percentage of suppressor/cytotoxic T-lymphocyte subsets in type 1 diabetes have been found to be altered. To determine whether thymosin and insulin in vitro have a role in improving or normalizing these abnormalities, PBMC from 28 patients with type 1 diabetes of various durations were treated with thymosin or insulin and the activity and the percentage of suppressor T cells were detected by using the method of ConA-induced suppressor T cells and WuT8 (suppressor/cytotoxic) monoclonal antibody respectively. Both thymosin and insulin were found to have ability to improve and normalize the ConA-induced suppressor cell activity and the percentage of WuT8 cells in diabetic patients. Data have shown that the lower the activity and the percentage of suppressor T cells, the more intense the effects of both compounds. The strongest effects were found at the concentrations of 10 micrograms/ml thymosin and 10 ng/ml insulin. Thymosin was more effective than insulin. This experiment also suggested that the activated lymphocytes stimulated by mitogens (PHA or ConA) were required when insulin exerted a significant effect on suppressor T cells. We conclude that thymosin and insulin in vitro can exert immuno-regulatory or immunostimulating effects on suppressor T cells.
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PMID:Effects of thymosin and insulin on suppressor T cell in type 1 diabetes. 146 83

It has been speculated that stressful life events can precipate some autoimmune diseases by altering the immune system. This study was undertaken to test this hypothesis in type I (insulindependent) diabetes. Thirty-two young patients (less than 40 years) with a recently diagnosed IDDM and 53 age-matched controls were interviewed according to a standardized questionnaire designed to identify, date, and weigh past stressful life events. In patients immunological status was assessed during the six months following the first manifestation of the disease by measuring anti-organ and anti-islet cell antibodies, T lymphocyte subsets, PHA mitogenic activity, IL2 production by blood mononuclear cells, IgG, IgA, IgM, and C3, C4 component fraction levels. The diabetic population experienced fewer life events, stressful or non-stressful, but in the 12 months preceding the onset of the disease, 50% of the diabetics endured at least one stressful life event as against only 18.8% of the controls (p less than 0.01). The only difference in the immunological status of the patients who had experienced a stressful life event in the previous twelve months and those that had not, involved PHA mitogenic activity which was significantly lower after a stressful event. While these findings do attest to a temporal relation between stress and type I diabetes in at least 1 out of 2 patients, they do not establish a causative connection.
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PMID:Stress antecedents and immune status in recently diagnosed type I (insulindependent) diabetes mellitus. 265 29

In order to analyze the first steps of T cell activation in type 1 diabetes we studied in vitro IL-2 and gamma-IFN production by peripheral blood mononuclear cells after 24 h PHA stimulation. There was a significant decrease in IL-2 production by mononuclear cells of the diabetic patients with respect to the controls. No significant difference was observed between the diabetic patients and the healthy subjects as regards gamma-IFN production. These observations may be interesting in relation to the pathogenetic mechanisms involved in type 1 diabetes. In particular, normal gamma-IFN production may indicate integrity of the natural killer circuit.
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PMID:Dissociated production of interleukin-2 and immune gamma-interferon by phytohaemoagglutinin stimulated peripheral mononuclear cells in type 1 (insulin-dependent) diabetes. 315 11

Production of and response to interleukin 2 (IL-2) were studied using peripheral blood mononuclear cells (PBMC) from 23 patients with type 1 diabetes. When compared to PBMC from 18 control subjects, mean PHA-stimulated IL-2 synthesis in the diabetic group was found unimpaired (1.2 +/- 0.1 vs 1.5 +/- 0.2 U/ml). However, 3 subgroups could be distinguished with regard to IL-2 synthesis: IL-2 production was significantly increased in 5 patients and decreased in 2 patients, while the remaining 16 diabetics produced normal levels of IL-2. The diabetic group displayed a curve of PBMC proliferation in response to a range of recombinant IL-2 which was not significantly altered. However, an abnormally high blastogenic response was detected in 5 patients, correlating to an increased percentage of Ia-bearing T lymphocytes, while a markedly low response was seen in 2 other patients. These alterations of the IL-2 system could be related duration of diabetes. Indeed, high synthesis of IL-2 was more frequent in patients with long-standing disease than in recent onset diabetics: 44% and 7%, respectively. Conversely, increased response to IL-2 was found more often in the latter group than in the former (28% vs 11%) while decreased sensitivity was seen only in the latter group (14%). No correlations were found between these results and basal or glucagon-stimulated C peptide levels, percent of glycosylated hemoglobin, presence of autoantibodies, lymphocyte subsets, or HLA typing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Production of and response to interleukin 2 by blood mononuclear cells from some type 1 diabetic patients. 349 40

IL-4 has been shown to protect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). To study IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore. IL-4 production by PBMC or T cells was strongly impaired in IDDM patients at diabetes onset (p < 0.0001). The mean IL-4 response of patients in the honeymoon stage was higher than the mean of the new onset patients, but significantly lower than the control group (p = 0.01). Patients with IDDM of longer duration (>2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; however, the difference was not statistically significant. IL-4 mRNA levels were measured using competitive reverse transcription PCR. The results showed greatly reduced mRNA levels in new onset IDDM. In contrast, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM. The results suggest an imbalance of inflammatory vs anti-inflammatory cytokine production at the onset of IDDM. Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabetes by allowing the inflammatory/autoimmune process in pancreatic islets to progress.
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PMID:Decreased IL-4 production in new onset type I insulin-dependent diabetes mellitus. 890 50

Cytokines secreted by antigen presenting cells, lymphocytes T and pancreatic beta cells are considered as the major mediators in the pathogenesis of IDDM. It has been suggested that cytokines released by macrophages/monocytes could have an initial role in beta-cell damage. The aim of the present study was the estimation of in vitro production of macrophage-derived cytokines: IL-1 beta, TNF-alpha, IL-12 by peripheral blood in high risk IDDM first degree relatives, since it could reflect early events leading to the development of type 1 diabetes in humans. The study was performed in 25 high risk IDDM subjects and 21 age and sex-matched healthy controls. IL-1 beta, TNF-alpha and IL-12 concentrations in supernatants of whole blood cultures with PHA (10 micrograms/ml) were quantified by ELISA. In the ICA positive relatives of IDDM subjects levels of IL-12 were significantly higher as compared with the control group, both at 48 h (p < 0.02) and at 72 h (p < 0.05) of incubation and positively correlated with TNF-alpha and IL-1 beta (R = 0.46, p < 0.02 and R = 0.32, p < 0.05). We did not observe statistical differences in in vitro production of TNF-alpha and IL-1 beta between the study groups. In conclusion we suggest that our findings support the hypothesis, that IL-12 is involved in the pathogenesis of human IDDM. If the involvement of Th1 cells is confirmed in the destruction of islet beta-cells, it is possible that IL-12 antagonists will have a role in the future prevention of insulin dependent diabetes mellitus.
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PMID:Increased in vitro interleukin-12 production by peripheral blood in high-risk IDDM first degree relatives. 917 25

We previously reported that a decreased TCR mediated activity of the GTP-GDP binding p21ras protooncogene is associated with prediabetes in non-obese diabetic (NOD) mice. Furthermore, prevention of autoimmune diabetes is associated with reversal of the p21ras signaling defect in NOD T cells. Based on these animal studies we determined the activation of p21ras in PBMC from patients with Insulin Dependent Diabetes Mellitus (IDDM), Non-Insulin Dependent Diabetes Mellitus (NIDDM) and normal healthy controls. Stimulation by PHA induced a decrease of 3.7 +/- 1.4% and an increase of 2.44 +/- 2.3%, p < 0.02 and 2.6 +/- 1.6%,p < 0.003 in the basal unstimulated p21ras activity in the IDDM, NIDDM and normal control groups, respectively. Expression of p21ras and its regulatory elements, the GTPase activating protein p120ras-GAP and the guanine nucleotide releasing factor (GNRF) hSOS, was comparable in the three groups. The in vitro proliferative response to PHA was comparable in the IDDM and control groups: stimulation index (SI) of 8.6 +/- 2.5 and 9.4 +/- 3.5 respectively, p < 0.44. No correlations were found in the IDDM patients between the degree of p21ras activation and the mitogen induced in vitro proliferative response or the various clinical parameters including age, gender, disease duration, daily insulin requirements and metabolic control. Taken together these data indicate that PBMC from IDDM patients are characterized by a persistent impairment in the activation of their p21ras. They also suggest that p21ras stimulated activity is a sensitive and independent parameter of PBMC activation in these patients.
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PMID:Defective activation of p21ras in peripheral blood mononuclear cells from patients with insulin dependent diabetes mellitus. 1043 77

The alterations of TGF-beta1 production are believed to contribute to the development of insulin-dependent diabetes mellitus (IDDM) in animal models as well as in humans. There is also increasing evidence about the role of this cytokine in the pathogenesis of diabetic vascular complications. The aim of our study was to evaluate in vitro TGF-beta1 production by peripheral blood of newly diagnosed type 1 diabetes patients and subjects in the pre-clinical stage of the disease in comparison to healthy controls and relatives of IDDM patients with low genetic risk for diabetes development. The study was carried out in three groups of subjects: 22 patients with a recently diagnosed type 1 diabetes, their 24 first degree relatives with a different genetic risk of IDDM development and 18 healthy volunteers (control group). In all studied groups whole blood was taken for morphology parameters. HbA1C and for 72 h cultures with PHA stimulation for the estimation of TGF-beta1 in vitro production. TGF-beta1 concentration in supernatants were quantified by ELISA. In the first degree relatives HLA typing (for DR3, DR4 and DQB1*0602 alleles), measurements of anti-pancreatic antibodies (ICA, GADA, IA-2A, IAA) and intravenous glucose tolerance tests were performed. The levels of TGF-beta1 in the supernatants were significantly higher in diabetic patients (P < 0.0002) and in their first degree relatives (P < 0.05) in comparison to the control group. In the group of first degree relatives TGF-beta1 levels were highest in subjects with the presence of two or more pancreatic autoantibodies and/or with impaired insulin release in IVGTT, but lowest in relatives with protective DQB1*0602 alleles (P < 0.01). There was also a significant positive correlation between the TGF-beta1 levels and HbA1C in the IDDM subjects and first degree relatives (P < 0.03). Our study suggests that the alterations of TGF-beta1 levels could be associated with the activity of autoimmune process leading to pancreatic B cells destruction and may have a role in the pathogenesis of diabetic complications, but further studies in humans are needed.
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PMID:The analysis of in vitro transforming growth factor-beta1 (TGF-beta1) production by peripheral blood in overt and pre-clinical type 1 diabetes mellitus. 1071 34

The 620Trp variant of the LYP protein, encoded by the lymphoid tyrosine phosphatase 22 gene (PTPN22), is associated with autoimmunity. In this study we aimed at characterising the role of this variant on lymphocyte activation. We analysed cytokine secretion and proliferation of peripheral blood mononuclear cells (PBMCs) and CD4(+)T cells in a cohort of clinically non-diabetic, multiple autoantibody-positive children, healthy controls and in children with type 1 diabetes (T1D). We found a decreased proliferation and IL-2 production of CD4(+)T cells after anti-CD3/anti-CD28 stimulation (p=0.04 for IL-2) among T1D patients. In addition, a profoundly decreased intracellular calcium flux in CD4(+)T cells after PHA stimulus was detected among 620Trp carriers. In contrast, no effect of this polymorphism on tuberculin and tetanus toxoid induced PBMC proliferation and cytokine secretion was observed in autoantibody positive children, healthy controls and children with newly-diagnosed T1D. In conclusion, the LYP 620Trp variant is associated with reduced activation, proliferation and IL-2 production in CD4(+)T cells among T1D patients. In accordance with our previous findings on the key role of this variant on disease progression, this mechanism is likely to contribute to the development of beta-cell specific autoimmunity.
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PMID:Reduced CD4+T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant. 1829 86

Cryopreserved peripheral blood mononuclear cells (PBMC) are commonly used when assessing immune responses in clinical trials, both for practical reasons and to minimize interassay variation, as samples are often collected and studied over time. This study investigated the effect of cryopreservation on cytokine and chemokine secretion, and on expression of regulatory T-cell associated markers, in samples from children with type 1 diabetes. PBMC were cultured before and after cryopreservation either with GAD(65) or PHA. Secretion of cytokines (IL-5, -6, -10, -12, -13 -17, IFN-gamma and TNF-alpha) and chemokines (IP-10, MCP-1, MIP-1alpha, MIP-1beta and RANTES) was analysed in cell supernatants using multiplex fluorochrome technique (Luminex). Expression of FOXP3 and TGF-beta mRNA was detected by multiplex real-time RT-PCR. Increased spontaneous secretion of IL-6, -10, -12, -13, IFN-gamma and MCP-1, and mRNA expression of FOXP3 and TGF-beta, was detected after cryopreservation. Stimulation with GAD(65) induced higher levels of IL-6, IFN-gamma, TNF-alpha and MIP-1alpha, whereas lower secretion was found for IL-10 and IL-13 in cryopreserved PBMC. Stimulation with PHA induced lower secretion of IP-10, MCP-1 and RANTES and FOXP3 mRNA expression after cryopreservation. Thus, cryopreserved PBMC were suitable to assess the immunological markers included in this study, even though their expression could differ from freshly handled cells.
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PMID:Cryopreserved peripheral blood mononuclear cells are suitable for the assessment of immunological markers in type 1 diabetic children. 1876 Oct 6


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