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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; islet cell antibodies ; fasting C-peptide ; insulin dosage ; prospective analysis ; fasting blood sugar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A cohort of 82 patients with Type 1 (insulin-dependent) diabetes was followed prospectively for 24 months, and 54 of them for 30 months, to study the relationship between fasting levels of immunoreactive C-peptide and titres of islet cell antibodies. After diagnosis, fasting C-peptide rose temporarily for 1–6 months of insulin therapy and declined continuously thereafter. While islet cell antibodies were present among 55% of the newly diagnosed patients, only 31% remained positive at 30 months. Their antibody titres decreased from 1∶81 at diagnosis to 1∶3. Only 3 patients (4%) who were islet cell antibody negative at diagnosis became positive later. The median C-peptide values among the persistently islet cell antibody positive patients decreased from 0.11 pmol/ml at 18 months, to 0.09 pmol/ml at 24 months, to 0.06 pmol/ml at 30 months compared to 0.18 (p=0.04), 0.15 (p=0.05) and 0.16 (p〈 0.003) pmol/ml, respectively, for the islet cell antibody negative patients. The median slope for the latter was −0.09 compared to −0.19 for the islet cell antibody positive patients (p=0.01). These differences were reflected in increasing dosages of insulin, since patients remaining antibody-positive for 30 months were given 1.3–1.4 times more insulin (p=0.01–0.004) than the antibody negative patients. This study demonstrates that islet cell antibodies may be a useful marker for predicting an increased rate by which endogenous B cell function is lost in Type 1 diabetes.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 195-203 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Mouse ; experimental diabetes ; streptozotocin ; H-2 system ; sex hormone ; insulitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five daily injections of streptozotocin (40 mg/kg) produced a delayed but progressively increasing level of hyperglycaemia in long term studies with male Naval Medical Research Institute mice and C3D2F1 (DBA 2 J male × C3H/ Tif female) F1 hybrid mice. The development of hyperglycaemia was paralleled by decreased amounts of pancreatic immunoreactive insulin as well as degranulation and necrosis of pancreatic B cells. Insulitis was found from days 9–25 after the first injection of streptozotocin. Compared with the F1 hybrid strain the parental inbred strains DBA 2 J and C3H/Tif demonstrated a certain resistance to streptozotocin. Development of hyperglycaemia did not differ in four congenic resistant lines of mice on the C57 BL/10 genetic background, indicating that major histocompatibility complex genes are not likely to determine susceptibility to streptozotocin-induced islet B cell damage.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 10 (1974), S. 431-438 
    ISSN: 1432-0428
    Keywords: Isolated islet cells ; ob/ob mouse islets ; islet disruption ; DNA content ; insulin release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pancreatic islets, isolated from the pancreas of obese-hyperglycemic mice, were used to prepare free islet cells in suspension. Batches of 100 islets were disrupted by mechanical shaking for 10 sec in a Ca2+-free HEPES-buffered Krebs-Ring'er medium containing 1 mM EGTA. From 200–500 islets, about 2.2×106 cells could be obtained in suspension, corresponding to a yield of roughly 55% as calculated from the content of DNA in cells and islets. The isolated islet cells appeared well-preserved in the light and the electron microscope and seemed to exhibit a high degree of viability as judged by viable cell counts, a radioactive assay for lysis and insulin release. Insulin release from islet cell suspensions, as calculated per cell, per content of DNA or insulin or per packed cell volume, was stimulated by glucose alone or in combination with theophylline. The glucose response was low compared with that of intact isolated islets.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Experimental diabetes mellitus ; glucose intolerance ; virus ; autoimmunity ; immune response genes ; islet-cell-surface antibody ; major histocompatibility locus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mice with different histocompatibility loci on an identical background genome (congenic resistant lines of mice) were used to study the possible influence of the histocompatibility complex on experimental diabetes. The major histocompatibility complex (H-2) was not found to influence the diabetogenic effect of encephalomyocarditis (EMC) virus. In contrast the glucose intolerance following heterologous and homologous immunization with pancreatic antigens appeared H-2 influenced. Antibodies against cell surface components on viable B-cells were present in serum from mice with glucose intolerance induced by homologous immunization. The results suggest that the susceptibility to experimental autoimmune diabetes in mice is influenced by the H-2 complex.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 22 (1982), S. 61-67 
    ISSN: 1432-0428
    Keywords: Insulin preparations ; porcine insulin ; bovine insulin ; human insulin ; recombinant DNA ; insulin gene ; polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusion Not only has recombinant DNA added another source of insulin for treatment, but also, and perhaps more important, it has allowed the development of new techniques for studying the structure and function of the B cell at the gene level. We can only hope that this information will bring us closer to the understanding of the disease, so the diabetic patient may benefit from other measures of treatment than the classical replacement therapy introduced by Banting and Best 60 years ago [47].
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; pancreatic B-cells ; serum cytotoxicity ; serum complement ; islet cell antibodies ; rubidium accumulation ; insulin release ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum from normal blood-donors and juvenile diabetic patients inhibited Rb+ accumulation and stimulated release of 51Cr and insulin in suspensions of dispersed pancreatic islet cells prepared from ob/ob mouse islets, which are rich in B-cells. The effects indicate the presence of a B-cytotoxic factor in human serum. Serum from mouse and fetal calf also inhibited the islet cell accumulation of Rb+. Toxicity was not suppressed by treating serum with protein A-Sepharose and did not correlate with islet cell binding of fluorescent antibodies to human immunoglobulin. Whereas all sera inhibited Rb+ accumulation, 3 of 6 diabetic patient sera, but no blood-donor serum, made the cells fluoresce on exposure to the fluorescent antibodies. Supporting a dependence on complement, toxicity remained after dialysis, but was destroyed by treating serum with zymosan-A or heating at 56 ° for 30 min.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Pancreatic islet cells ; cell suspensions ; islet cell surface antibodies ; cell surface immunofluorescence ; Protein A radioassay ; cell surface antigens ; autoimmunity ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rabbits were immunised with suspensions of viable, insulin-producing islet cells prepared from collagenase-isolated rat or ob/ob mouse pancreatic islets. Antibodies reactive with the surface of dispersed rat islet cells were present in both the rabbit anti-rat and the rabbit anti -ob/ob mouse islet sera as revealed by indirect immunofluorescence or by a radioligandassay using 125I-Protein A as a measure of cell bound IgG. In a competition assay the binding of 125I-Protein A was displaced in a concentration dependent manner by non-radioactive Protein A. Maximal displacement was found at concentrations of Protein A higher than 0.1 μg. added to 105 islet cells. Although not always detected by immunofluorescence there was a several-fold increase above normal rabbit serum of 125I-Protein A-binding to rat hepatocytes and spleen lymphocytes incubated with the islet cell antisera. Conversely, rabbit antisera against rat spleen lymphocytes or against a rat liver plasma membrane preparation reacted with rat islet cells. The rabbit anti-rat islet cell antiserum was absorbed to both spleen lymphocytes and hepatocytes until there was no binding of 125I-Protein A to either cell type. Islet specific antibodies were still present since this doubly absorbed antiserum induced cell surface immunofluorescence as well as 125I-Protein A-binding to rat islet cells. It is concluded that apart from common antigenic determinants immunisation with viable islet cells induces formation of antibodies directed against specific islet cell surface components.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes ; islet cell antibodies ; islet cell surface antobodies ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islet cell cytoplasmic and cell surface antibodies along with other autogenic tissue antibodies were determined prospectively from the day of diagnosis of insulin-dependent diabetes in a group of children and adolescents. Prior to the initiation of insulin therapy 30 out of 33 were antibody-positive, 67% having islet cytoplasmic antibodies and 67% islet cell surface antibodies. Among 74 age- and sex-matched non-diabetic individuals 1% had islet cell cytoplasmic antibodies and 3% had islet cell surface antibodies. A prospective analysis in 17 patients showed a diminishing prevalence of islet cell antibodies with increasing duration of diabetes. Islet cell cytoplasmic or cell surface antibodies were found independently of each other or in combination and with various patterns of persistence. The results indicate a strong association of islet cell antibodies with the onset of insulin-dependent diabetes in childhood and adolescence.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Mouse ; experimental diabetes ; streptozotocin ; sex influence ; sex hormone ; islet cell cytotoxicity in vitro ; lymphocyte transfer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of sex on pancreatic islet B cell susceptibility to streptozotocin was studied in mice given multiple low doses of streptozotocin. Male C3 D2 F1 mice developed a steadily increasing blood glucose level after a lag period of about 3 weeks, in contrast to females who were resistant. Spleen cells from streptozotocin treated female animals produced hyperglycaemia in total body irradiated syngeneic female recipients, but only if the recipients were treated with testosterone. Testosterone treatment of donors did not affect blood glucose levels of recipients. Streptozotocin cytotoxicity in vitro determined by a 51Cr-release assay revealed an increased sensitivity to streptozotocin in dispersed islet cells from adult male animals as compared with cells from adult female mice. The incubation of islet cells from animals of either sex with testosterone, or oestradiol plus progesterone, did not enhance the susceptibility to streptozotocin. Islet cells from sexually immature male or female mice were less susceptible to streptozotocin. The results demonstrate that sex determines susceptibility to streptozotocin in vivo and in vitro.
    Type of Medium: Electronic Resource
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