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Mouse embryonic stem (ES) cells differentiate into cells of all three primary germ layers including endodermal cells that produce insulin in vitro. We show that constitutive expression of Pax4 (Pax4(+)), and to a lesser extent Pdx1 (Pdx1(+)), affects the differentiation of ES cells and significantly promote the development of insulin-producing cells. In(More)
IDDM results from immune-mediated destruction of insulin-producing pancreatic beta-cells in individuals genetically susceptible for the disease. There is evidence that the 65-kDa isoform of GAD plays a critical role in the induction of autoimmune diabetes in NOD mice. In humans, it is still unclear when and to what beta-cell antigens autoreactive(More)
OBJECTIVE To determine whether screening for the presence of multiple antibody markers for IDDM is effective at identifying individuals with high risk for disease development. RESEARCH DESIGN AND METHODS Antibodies to GAD and the tyrosine phosphatase-like protein 1A-2 were determined in sequential serum samples from 44 first-degree relatives of IDDM(More)
Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with(More)
Sera from 114 first-degree relatives of insulin-dependent diabetes mellitus (type I diabetes) patients and 81 healthy individuals living in Germany were analyzed for antibodies to rat brain glutamic acid decarboxylase (GAD-ab) using an immunoprecipitation assay. The determination of GAD-ab in the 81 islet cell antibody (ICA) and insulin autoantibody (IAA)(More)
Aims/hypothesis. Glima 38 is an N-glycated neuroendocrine membrane protein of Mr 38 000, which is recognised by autoantibodies in approximately 20 % of patients with Type I (insulin-dependent) diabetes mellitus. The aim of this study was to characterise the carbohydrate moiety and generate peptide maps of glima 38. Methods. Sera of high immunoreactivity to(More)
To investigate the impact of diabetic mothers on the maturation of the immune system in their offspring, immunophenotypic markers of major lymphocyte subpopulations were evaluated by two-colour flow cytometric analysis in 160 healthy children of diabetic mothers (100 with insulin-dependent diabetes mellitus (IDDM); 48 with gestational diabetes), including(More)
OBJECTIVE To evaluate the association of antibodies to glutamic acid decarboxylase (GAD-ab) and diabetic complications (neuropathy, retinopathy, and nephropathy) in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS We examined the prevalence of GAD-ab (immunoprecipitation assay) and islet cell antibodies (ICAs)(More)
For the prediction of type I diabetes in first degree relatives of type I diabetics, a variety of laboratory methods are now available. Thus, screening for serum antibodies against the body's own insulin, islet cells and the enzyme glutamate decarboxylase, represents a simple and well-established routine examination used for early diagnosis. The combination(More)