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  • 1
    ISSN: 1432-0428
    Keywords: Pregnancy ; B-cell volume ; insulin ; Wistar rats ; streptozotocin administration ; islets ; DNA synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of pregnancy on pancreatic insulin content and relative B-cell volume has been studied in normoglycaemic Wistar rats treated with streptozotocin 14 days before mating. A single intravenous injection of streptozotocin (30 mg/kg body weight) caused a significant reduction of pancreatic insulin content and B-cell volume. The islet insulin content was 60% of control values. However, pregnancy-associated adaptation was preserved in these streptozotocin-treated animals. Plasma insulin levels, pancreatic insulin and B-cell volume were significantly enhanced compared with non-pregnant rats investigated on the same date. The incorporation of [3H]-thymidine into islets from pregnant rats (day 10.5) was higher than that in islets isolated from non-pregnant animals. After delivery insulin content and B-cell volume returned to pre-pregnant values. Also during a longer period after streptozotocin treatment (156 days), no measurable enhancement of B-cell volume and pancreatic insulin content was observed indicating the unresponsiveness of residual B cells to compensate spontaneously for the loss despite persisting normoglycaemia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Monoclonal islet cell surface antibodies (mcICSA) ; anti-islet cell toxicity ; application in vivo ; pancreatic insulin content ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two monoclonal Beta-cell surface antibodies M10H6 und K14D10 were obtained by fusion of spleen cells of Balb/c mice with the myeloma cell line P30. The monoclonal antibody M10H6 was induced by immunization with rat insulinoma cells finally boostered with disintegrated rat islets, whereas the K14D10 was generated after immunization with porcine proinsulin. Both monoclonals belong to the IgG2A isotype and were screened with insulin-producing rat insulinoma cells by an indirect immunofluorescence test as well as by a cellular enzyme linked immunosorbent assay. In addition to the cell surface binding on living Beta cells the monoclonals react with islets on cryostat sections of rat pancreas. The anti-islet cytotoxic potential of these monoclonals was measured by 51Chromium-release in the presence of complement or Fc-receptor bearing leucocytes using 51Chromium-labelled rat islet cells as target. Both antibody secreting hybridomas were propagated in syngeneic mice resulting in high levels of islet cell surface antibodies in ascites and sera from the recipient. High anti-islet cytotoxicity was mediated by ascites fluid, but no mouse developed hyperglycaemia. Furthermore, the repeated injections of the monoclonals into rats did not exert a diabetogenic action and failed to reduce the pancreatic insulin content although the attraction of the K14D10 to the pancreatic islets in vivo could be demonstrated. We conclude that islet cell surface antibody-mediated Beta-cell lysis in vitro may not be relevant to Beta-cell destruction in vivo.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Pancreatic islet allograft ; immunotherapy ; anti-IL-2 RMAB ; cyclosporin, graft histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since interleukin-2-receptor expressing cells play a role in allograft rejection, we investigated the effect of anti-interleukin-2 receptor monoclonal antibody treatment on graft survival of allografted pancreatic islets. When pancreatic islets obtained from Lewis A-rats (haplotype RT1a) were grafted under the kidney capsules of streptozotocin-diabetic Lewis rats (haplotype RT1u), the recipients relapsed into hyperglycaemia within 11 days (7±1 days). Treatment of the recipient rats with low-dose cyclosporin (1.5 mg/kg body weight) had no effect on allograft survival (9±1 days). The application of anti-interleukin-2 receptor monoclonal antibody (1mg/kg body weight) for 10 days resulted in a prolongation of allograft survival (42.5±15.3,p〈0.01). In 3 out of 11 animals a permanent normoglycaemia (〉120 days) associated with glucose intolerance was observed. When the recipients were treated for 10 days with cyclosporin and anti-interleukin-2 receptor monoclonal antibody, the allograft survival was also prolonged (45.1±14.6,p〈0.01); again 3 out of 11 animals remained permanently normoglycaemic while exhibiting a normal glucose tolerance.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2277
    Keywords: Pancreas transplantation, fetal, rat ; Fetal pancreas transplantation, rat ; Graft rejection, pancreas, fetal ; Rejection, pancreas, fetal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of 17.5- to 18.5-day-old fetal pancreases were grafted under the kidney capsule of streptozotocin-diabetic rats. Eight syngeneically grafted glands were sufficient to reverse the diabetes of the recipients within 4 weeks when the recipient rats were treated with insulin for 18 days after transplantation. Eight allogeneic fetal pancreases obtained from one donor strain were rejected after transplantation and the recipients relapsed into hyperglycemia immediately after insulin withdrawal. Eight allogeneic fetal pancreases obtained from eight MHC-different donor strains were also rejected and the recipients relapsed into hyperglycemia after insulin withdrawal. Using fetal pancreases as tissue sources, the combination of the allogeneic graft from different donor strains was not sufficient to prolong the survival time of the grafted tissue.
    Type of Medium: Electronic Resource
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