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)

Several lines of evidence suggest the involvement of the human endogenous retrovirus (HERV)-K18 in the etiology of type 1 diabetes. HERV-K18 encodes for a T-cell superantigen (SAg). T-cells with T-cell receptor Vbeta7 chains reactive to the SAg and HERV-K18 mRNA were enriched in the tissues at the onset of the disease. HERV-K18 transcription and SAg function in cells capable of efficient presentation are induced by proinflammatory stimuli such as viruses and interferon-alpha and may trigger progression of disease to insulitis or from insulitis to overt diabetes. Allelic variation of HERV-K18 or the DNA flanking it, the CD48 gene, could modulate genetic susceptibility. Analysis of 14 polymorphisms in the locus using 754 diabetic families provided positive evidence of association of three variants belonging to a single haplotype (P = 0.0026), present at 21.8% frequency in the population. Genotype analysis suggested a dominantly protective effect of this haplotype (P = 0.0061). Further genetic and functional analyses are required to confirm these findings.
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PMID:Association of human endogenous retrovirus K-18 polymorphisms with type 1 diabetes. 1498 74

Accumulating evidence that granulocyte colony-stimulating factor (G-CSF), the key hematopoietic growth factor of the myeloid lineage, not only represents a major component of the endogenous response to infections, but also affects adaptive immune responses, prompted us to investigate the therapeutic potential of G-CSF in autoimmune type 1 diabetes. Treatment with G-CSF protected NOD mice from developing spontaneous diabetes. G-CSF triggered marked recruitment of dendritic cells (DCs), particularly immature CD11c(lo)B220(+) plasmacytoid DCs, with reduced costimulatory signal expression and higher interferon-alpha but lower interleukin-12p70 release capacity than DCs in excipient-treated mice. G-CSF recipients further displayed accumulation of functional CD4(+)CD25(+) regulatory T-cells that produce transforming growth factor-beta1 (TGF-beta1) and actively suppressed diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. G-CSF's ability to promote key tolerogenic interactions between DCs and regulatory T-cells was demonstrated by enhanced recruitment of TGF-beta1-expressing CD4(+)CD25(+) cells after adoptive transfer of DCs isolated from G-CSF- relative to vehicle-treated mice into naive NOD recipients. The present results suggest that G-CSF, a promoter of tolerogenic DCs, may be evaluated for the treatment of human type 1 diabetes, possibly in association with direct inhibitors of T-cell activation. They also provide a rationale for a protective role of the endogenous G-CSF produced during infections in early diabetes.
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PMID:Treatment with granulocyte colony-stimulating factor prevents diabetes in NOD mice by recruiting plasmacytoid dendritic cells and functional CD4(+)CD25(+) regulatory T-cells. 1561 13

Development of type 1 diabetes has been attributed to T-cell-mediated autoimmunity, which is regulated by antigen-presenting cells. To study the role of liver-derived B220(+) regulatory dendritic cells (DCs) in the development of diabetes in non-obese diabetic (NOD) mice, we found that liver 220(+) DCs could easily be propagated from young NOD mice, but that such propagation was extremely difficult from mice older than 11 weeks, when insulitis began. This was not simply an age-related phenomenon, because liver B220(+) DCs were readily propagated from both young and old congenic non-obese diabetic-resistant (NOR) and normal BALB/c mice. It was therefore speculated that the development of diabetes might be associated with a lack of precursors of B220(+) DC in the liver in this animal model. Unfortunately, the specific marker for precursors of liver B220(+) DC has not been identified. An alternative approach to supplement liver B220(+) DCs by intravenous administration significantly inhibited the development of diabetes by inducing T-cell hyporesponsiveness via enhancement of their apoptotic death. Liver B220(+) DCs were capable of effectively presenting antigens but, unlike plasmacytoid DCs, did not express CD11c and were not interferon-alpha producers. These observations may throw new light on the aetiopathology of type 1 diabetes.
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PMID:The role of liver-derived regulatory dendritic cells in prevention of type 1 diabetes. 1723 42

A novel pigmented dermatosis was observed in four unrelated boys, three of whom had insulin-dependent diabetes. Three patients were the offspring of consanguineous parents. All four boys had pigmented hypertrichotic patches or induration on the upper inner thighs, with variable involvement of the genitalia, trunk, and limbs. Two boys had episcleritis and orbital proptosis with similar facies and musculoskeletal abnormalities including clinodactyly, flat feet, and short stature. One child had paraaortic and inguinal lymphadenopathy and three patients had an enlarged liver and spleen. A large, swollen pancreas was observed on ultrasound imaging in one patient with insulin dependent diabetes who also had echocardiographic evidence of pericardial inflammation. Three boys had elevated laboratory markers of inflammation. Biopsy specimens from the skin and orbit showed a chronic inflammatory cell infiltrate composed of polyclonal lymphocytes, histiocytes, and plasma cells; fibrosis was observed in two patients, one of whom had previously received radiation therapy to the orbit. Two boys responded to treatment with subcutaneous interferon-alpha, combined with a short course of oral prednisone in the child without diabetes. We believe these inflammatory pigmented skin lesions represent a unique dermatosis associated with diabetes mellitus and systemic disease. The pathogenesis is unknown. The presence of consanguinity in three of four families, and similar dysmorphic features in two boys, suggest a genetic disorder, possibly with autosomal recessive inheritance.
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PMID:Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder? 1746 1

We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-alpha) 2b. The patient presented with polydipsia, polyuria, hyperglycemia, diabetic ketoacidosis, combined with C-peptide secretion deficiency and positive islet cell autoantibody (ICAb). IFN-alpha 2b treatment was terminated and instead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-alpha 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-alpha is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-alpha therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.
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PMID:Abrupt onset of type 1 diabetes mellitus during recombinant interferon-alpha 2b therapy in a patient with chronic hepatitis B. 1869 91

Viral infection has been hypothesized to be one of the environmental triggers for the development of type 1 diabetes. Infection induces a large amount of interferon-alpha (IFN-alpha) produced by dendritic cells and other cells. To test the role of IFN-alpha in the development of diabetes, we have used three different experimental approaches in both diabetes-prone and -resistant animal models for type 1 diabetes. Our results suggested that a viral mimic or IFN-alpha can either suppress or promote the development of autoimmune diabetes, depending on the model system. It is likely that IFN-alpha plays a complex role in the etiology of type 1 diabetes.
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PMID:IFN-alpha can both protect against and promote the development of type 1 diabetes. 1912 Feb 92

Combined pegylated interferon and ribavirin therapy for chronic hepatitis C infection cause a wide range of side effects, including flu-like syndrome, hematological abnormalities, cardiovascular symptoms, gastrointestinal symptoms, pulmonary dysfunction, depression, and retinopathy. Interferon-alpha has been shown to be related to the development of various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroid disease, and type 1 diabetes mellitus (DM). Type 1 DM and thyroid disease respectively develop in 0.08-2.61% and 10-15% of patients treated with combined interferon-alpha and ribavirin for chronic hepatitis C. The coexistence of type 1 DM and autoimmune thyroiditis was rarely reported. We report a case of a 33-year-old female patient with chronic hepatitis C who simultaneously developed diabetic ketoacidosis and autoimmune thyroiditis after treatment with pegylated interferon-alpha 2b and ribavirin.
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PMID:[Occurrence of diabetic ketoacidosis and autoimmune thyroiditis in a patient treated with pegylated interferon-alpha 2b and ribavirin for chronic hepatitis C]. 2060 4


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