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  • 1
    ISSN: 1432-0428
    Keywords: Obese-hyperglycaemic mice ; isolated pancreatic islets ; islet transplantation ; serum glucose ; islet volume ; autoradiography ; islet cell replication ; immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Implantation of allogeneic pancreatic islets encapsulated in Millipore diffusion chambers has been reported to normalize the obese-hyperglycaemic syndrome in mice. In the present study, both young and adult ob/ob mice remained hyperglycaemic and gained weight after intrasplenic implantation of 500 isogeneic islets isolated from lean mice. Such islets normalized the elevated blood-glucose of alloxan-diabetic lean mice. Morphometric analysis of the intrasplenically implanted islets showed that the mean islet volume in the ob/ob mice was five times larger than that of the lean, non-diabetic mice. Immunocytochemical staining of the spleens showed an increased proportion of B-cells in the enlarged, intrasplenic islets in the ob/ob mice. Moreover, autoradiographical examination of these islets demonstrated the presence of several labelled cells. These results suggest that the growth of the implanted “lean” islets is due to extrapancreatic factors which stimulate islet cell replication in the obese-hyperglycaemic mouse.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 23 (1982), S. 525-528 
    ISSN: 1432-0428
    Keywords: Diabetes ; rat pregnancy ; islets of Langerhans ; B cell proliferation ; diabetic fetopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since it has not been possible to reproduce, in the rat, the hyperplasia of the islets of Langerhans observed in the fetus in human diabetic pregnancy, the rate of proliferation of the endocrine pancreas of fetuses of manifest diabetic rats has been studied. Rats were rendered diabetic by streptozotocin injections before mating. At days 20 or 22 of gestation the pregnant rats were injected with colchicine and sacrificed at 1-h intervals. The mitotic indices of the fetal endocrine pancreas were determined and plotted against the time after colchicine injection. The production of new cells (i.e. the cell birth rate) was estimated from the slopes of the regression lines. On both days 20 and 22 of gestation, the cell birth rates of the endocrine pancreas of the fetuses of manifest diabetic mothers were only one-third of the control values obtained in normal, age-matched fetal pancreas (daily cell birth rate = 10%). This finding corresponds to the previous observation of a low B cell mass in the offspring of diabetic rats. The results indicate that the growth and development of the fetal endocrine pancreas is retarded in manifest diabetic pregnancy in the rat.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 27 (1984), S. 464-467 
    ISSN: 1432-0428
    Keywords: Inbred mouse strains ; alloxan diabetes ; islet culture ; islet implantation ; islet cell replication ; autoradiographic labelling index ; proinsulin biosynthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Proliferation of islet cells may compensate for both an increased peripheral insulin resistance and islet cell destruction but the capacity for regeneration may be genetically determined. For the latter reason, glucose-stimulated islet cell replication was estimated in both inbred C57BL/6J (BL/6) and C57BL/KsJ (BL/Ks) mice. Islets isolated from both strains were exposed to high concentrations of glucose in vitro or in vivo for a prolonged time period. This was achieved either by culturing the islets free-floating in a high glucose concentration medium for 3 days or implanting the islets intrasplenically in insufficient numbers to cure alloxan-diabetic syngeneic recipients. In both strains high glucose concentration culture was found to increase the autoradiographic labelling index of the islets but the replicatory activity decreased with age. The proliferative rate of the islet cells of the BL/6 mice was about twice as high as that of the BL/Ks mice irrespective of age and glucose concentration. Likewise, the labelling index of intrasplenic BL/6 islets implanted into alloxan-diabetic mice was twice as high as that of the islets implanted into alloxan-diabetic BL/Ks mice. The replicatory activity of the latter islets did not differ statistically from that of islets implanted into non-diabetic control BL/Ks mice. No differences in the rates of proinsulin and total protein biosynthetic rates were observed between high glucose concentration-cultured islets of the two mouse strains. The present results indicate that the proliferative response of pancreatic islets to a prolonged glucose stimulation may be genetically determined. This may play a significant role in the development of different diabetic syndromes both in laboratory animals and man.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 25 (1983), S. 444-447 
    ISSN: 1432-0428
    Keywords: Alloxan ; DNA repair ; dimethyl urea ; pancreatic islets ; poly(ADP-ribose)synthetase ; streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present investigation, the abilities of streptozotocin and alloxan to induce DNA repair synthesis in isolated mouse pancreatic islets have been compared using an autoradiographic technique. Streptozotocin exposure in vitro induced a dose-dependent DNA repair synthesis, whereas no such effect was observed after alloxan treatment. The hydroxyl radical scavenger dimethyl urea and the poly(ADP-ribose) synthetase inhibitors nicotinamide and theophylline reduced the streptozotocin-induced DNA repair. The results suggest that the initial events in streptozotocin-induced B cell injury are DNA damage and repair and that alloxan exerts its major cytotoxic effect by a different mechanism.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Bioscience reports 2 (1982), S. 867-876 
    ISSN: 1573-4935
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The regulatory role of cyclic AMP (cAMP) in the growth and insulin production of the islet organ in vitro has been investigated. The effects of dibutyryl cyclic AMP (dbcAMP), theophylline , and 3-isobutyl-1-methylxanthine (IBMX) on DNA replication and on the biosynthesis of RNA and insulin in fetal rat islets of Langerhans maintained in tissue culture have been studied. Raising the glucose concentration from 2.7 mM to 16.7 mM caused a two-fold increase in DNA replication. Both dbcAMP and theophylline markedly inhibited the DNA replication at all glucose Concentrations studied. Low concentrations of IBMX stimulated DNA synthesis. However, at higher concentrations of this drug, known to considerably increase the islet cAMP levels , a marked inhibition of islet DNA replication was observed. Both (pro)insulin and total protein biosynthesis were stimulated by glucose, whereas dbcAMP stimulated only the (pro)insulin biosynthesis. Since glucose is known to raise islet intracellular levels of cAMP, which is known to be an inhibitor of cellular proliferation, the observed glucose stimulation of both islet-cell DNA replication and insulin production appeared conflicting. It is suggested that this dual effect of glucose may depend on a stimulation of proliferation in a limited pool of islet cells which may not exhibit an increase in cAMP.
    Type of Medium: Electronic Resource
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