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  • 1
    ISSN: 1432-0428
    Keywords: Diabetes ; EMC virus ; DBA2 mice ; islets of Langerhans ; ultrastructure ; insulin ; glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Infection of DBA2 mice with the M strain of EMC virus was used to study the effects of virusinduced diabetes on the A and B cells of the islets of Langerhans. A transient hypoglycaemia was seen in 48% of mice 2–3 days after infection and probably resulted from increased serum insulin concentrations together with inhibition of glucagon secretion at that time. Islets from hypoglycaemic mice showed no significant alterations from control level in basal or fluoride-stimulated adenylate cyclase activity. Overall, 70% of infected mice became hyperglycaemic with a maximum incidence 6 days after infection. Hyperglycaemia was accompanied by a dramatic reduction in the total pancreatic insulin content and in insulin secretory responses to glucose and theophylline, while A-cell structure and function appeared relatively unaffected in diabetic animals. Basal adenylate cyclase activity was increased in hyperglycaemic mice at 7 days after infection, while fluoride-stimulated adenylate cyclase activity was normal throughout the course of infection. Ultrastructural alterations were observed in a small proportion of B cells from two days after infection and included abnormalities of mitochondrial structure and increased electron opacity of the cytoplasm of affected cells, which subsequently led to complete necrosis. The results suggest that EMC virus specifically affects the B cells of the islets and that disturbances of A cell function may be secondary to B cell damage.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Transplantation ; islets of Langerhans ; streptozotocin diabetes ; diffusion chambers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islets of Langerhans have been enclosed in polycarbonate diffusion chambers and transplanted intraperitoneally to syngeneic streptozotocin diabetic rats. Direct implantation of 1100–1400 islets in these chambers failed to reverse diabetes during a period of 12 weeks, and viable islet tissue was not recoverable at the end of this period. Islets placed in chambers which had been implanted 3–12 weeks previously similarly failed to lower blood glucose of diabetic recipients, as a result of lack of survival of the islets. Insulin infusion into chambers previously implanted in vivo, I125 insulin diffusion studies in chambers recovered 6–8 weeks after implantation, and scanning electron microscopy of the recovered membranes all indicated that the pores were not totally occluded. The failure of islet transplantation via chambers in this simple syngeneic model has discouraging implications for their use as a means of avoiding allograft rejection.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta diabetologica 30 (1993), S. 99-104 
    ISSN: 1432-5233
    Keywords: Insulin synthesis ; Islet of Langerhans ; Northern blotting ; Phorbol ester ; Protein kinase C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Activation of protein kinase C (PKC) by the phorbol ester 4β-phorbol myristate acetate (4β-PMA) stimulated (pro)insulin biosynthesis in collagenase-isolated rat islets of Langerhans, as assessed by measuring the incorporation of [35S]cysteine into proinsulin and insulin after fractionation by high performance liquid chromatography. The stimulatory effects of 4β-PMA were observed at a substimulatory concentration of glucose (2 mM) but were not additive to the stimulatory effects of 20 mM glucose on insulin biosynthesis. Prolonged exposure to 4β-PMA caused a marked down-regulation of PKC activity in islets. PKC-depleted islets showed a much reduced biosynthetic response to 20 mM glucose, but this was caused, at least in part, by an enhanced basal rate of (pro)insulin synthesis. These elevations in the basal rate of insulin synthesis were not secondary to an inerease in the amount of preproinsulin mRNA in PKC-depleted islets since Northern blot analysis showed that prolonged exposure to 4β-PMA, and the subsequent loss of PKC activity, did not detectably alter basal levels of preproinsulin mRNA. These results suggest that the activation of PKC stimulates (pro)insulin synthesis in rat islets by enhancing translation of existing preproinsulin mRNA, and that this may play some part in the biosynthetic responses of β-cells to glucose.
    Type of Medium: Electronic Resource
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