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  • 1
    ISSN: 1432-0428
    Keywords: Neonatal hypoglycemia ; hyperinsulinism ; leucine-sensitivity ; islet hyperplasia ; ultrastructure ; A ; B ; D and type IV cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphometric and ultrastructural studies were performed on biopsy material from the pancreas of an infant with severe leucine-sensitive hypoglycemia and hyperinsulinism, in whom no insulinoma had been found. Qualitatively many large B cells were observed within the pancreatic islets. Quantitatively an about two fold increase of islet tissue proportion (4.2%) was demonstrated, compared with controls of approximately the same age (1.8%). Differential islet cell counting revealed an increase in A1 cells whereas the percentage of A2 and B cells appeared to be unchanged. Ultrastructurally in addition to A, B, and D cells a fourth islet cell type was demonstrated in unusual frequency. Its general function and its particular significance for the hypoglycemic syndrome are unknown. The findings correspond well with recent observations on the islet cell system in cases of neonatal hypoglycemia with leucine-sensitivity and hyperinsulinism.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 12 (1976), S. 227-235 
    ISSN: 1432-0428
    Keywords: Sulfonylureas ; insulin secretion ; B-cells ; calcium demonstration ; calcium localization ; histochemistry ; ultracytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The study examines the effects of sulfonylurea compounds on the histo- and ultracytochemical calcium distribution within the B-cells of mice using the glyoxal-bis-(2-hydroxyanil) (GBHA) and the pyroantimonate method combined with X-ray microanalysis. Treatment with tolbutamide (200 mg/kg), glibenclamide (2 mg/kg) and glisoxepide (2 mg/kg), causing moderate hypoglycemia and B-cell degranulation, was associated with an unchanged (30, 90 min) or slightly increased (180, 360 min, 4, 42 d) GBHA staining intensity of the islet cells compared with controls. Ultra-cytochemically sulfonylureas provoked, compared with controls, a redistribution of calcium-rich, electron dense pyroantimonate precipitates (EDPP). Precipitation predominantly occurred along the inner surface of the plasma membranes and within the granule halos. In contrast, the cytoplasmic matrix, the Golgi complexes and the rough endoplasmic reticulum contained only few fine precipitates. — The sulfonylureas investigated exerted identical effects on the histo- and ultracytochemical calcium distribution in B-cells. — The results indicate that sulfonylurea-induced insulin secretion is associated with an accumulation and redistribution of calcium within the B-cells. This supports the hypothesis that an altered calcium handling by the B-cell mainly accounts for the insulinotropic effect of sulfonylureas.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 45 (1989), S. 352-355 
    ISSN: 1420-9071
    Keywords: Cytoprotection ; cyclosporin ; endocrine pancreas ; insulin-secretion ; electron microscopy ; prostaglandin analogue ; rioprostil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E1 analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days. At toxic doses of cyclosporin (10 and 20 mg/kg b.wt), the B-cells showed severe hydropic degeneration of the endoplasmatic reticulum and slight degranulation of the B-cells. Accordingly, the insulin secretion was markedly impaired. Administration of rioprostil ameliorated the insulin secretion significantly, but not the ultrastructural changes. At therapeutic levels of cyclosporin (5 mg/kg b.wt), the hydropic degeneration and the drop in insulin secretion were completely prevented by rioprostil. This observation might have therapeutic implications in the treatment of patients, in particular those undergoing pancreatic transplantation.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Transplantation ; diabetes mellitus ; islet cells ; BB rats ; cyclosporin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ability to prepare purified islet Beta-cell aggregates was used to examine the survival of this cell type after allotransplantation in diabetic BB rats. The aggregates were intraportally implanted in numbers that were previously found to correct a streptozotocin-induced diabetic state in syngeneic or allogeneic Brown Norway recipients. When the grafts were prepared from RT1u/l donors, which shared the MHC-class I antigen with the BB recipients (RT1u/u), their implant sites became diffusely infiltrated by inflammatory cells and their metabolic function was completely lost within 5 weeks. MHC-class I incompatible islet Beta-cell allografts (RT1n/n) exhibited a longer survival, in particular when combined with other islet endocrine cells and/or when covered by a 5-week cyclosporin treatment. In the latter combination, 10 of 12 BB rat recipients remained normoglycaemic over the 10-week observation period, their liver implants presenting a comparable insulin reserve and similarly discrete mononuclear cell infiltration as streptozotocin-diabetic Brown Norway rats receiving this treatment. However, administration of cyclosporin to diabetic BB rats was associated with a morbidity that was not observed in drug-treated streptozotocin-diabetic Brown Norway animals or in untreated diabetic BB rats. It is concluded that MHC-incompatible islet Beta cells can induce a long-term normalization in diabetic BB rats provided that they are implanted under conditions which allow allograft acceptance. The standardized preparation of purified islet Beta-cell grafts can help assessing the conditions for successful transplantations in diabetes with an autoimmune origin.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 38 (1995), S. 1405-1411 
    ISSN: 1432-0428
    Keywords: Pancreatic duct ligation ; duct-cell differentiation ; beta-cell neogenesis ; immunocytochemistry ; morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the growth of islet beta and alpha cells in adult rats which had undergone partial pancreatic duct ligation. Whereas the non-ligated head portion of the pancreas remained unaffected in terms of histology and cell population dynamics, the ligated tail part of the pancreas showed pronounced changes in histology and cell growth. These changes included replacement of exocrine acini by ductal complexes and significant growth of islet cells. Using immunocytochemistry and morphometry, we found that the beta-cell population had nearly doubled within 1 week and that a smaller, but also significant growth of the alpha-cell population had occurred. In addition, small islets and islet-cell clusters were more numerous in the pancreatic tail, indicating islet neogenesis. The bromodeoxyuridine (BrdU) pulse labelling index of beta and alpha cells increased five fold and threefold, respectively, in the tail. However, the observed beta-cell labelling index remained below 1% which was largely insufficient to explain the increased number of beta cells. This indicates that recruitment from a proliferating stem-cell compartment was the main source for the beta-cell hyperplasia. A tenfold-elevated BrdU labelling index (18%) was observed in the duct-cell compartment which was identified by specific immunostaining for cytokeratin 20. Transitional cytodifferentiation forms between duct cells expressing cytokeratin 20 and beta cells expressing insulin, or alpha cells expressing glucagon, were demonstrated by double immunostaining. Pancreatic duct ligation also induced the expression of the beta-cell-specific glucose transporter type 2 (GLUT-2) in duct cells, indicating their metaplastic state. We concluded that in this adult rat model, the proliferation and differentiation of exocrine duct cells represents the major mechanism of endocrine beta-cell neogenesis. Our study thus demonstrates that in normal adult rats islet-cell neogenesis can be reactivated by stimulation of pancreatic duct cells.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 185-190 
    ISSN: 1432-0428
    Keywords: Histological alterations ; exocrine pancreas ; endocrine pancreas ; insulitis ; periductulitis ; tolerance to insulin ; insulin antibodies ; cellular immune reaction ; crystalline insulin ; chromatographed insulin ; monocomponent insulin ; fractions of insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mice immunized with once crystallized or chromatographed insulin at various doses throughout a period of three months, in order to investigate “tolerance induction” to different insulin preparations, unexpectedly revealed lymphocytic infiltrates in the endocrine and exocrine pancreas. Peri-insulitis, periductulitis and sometimes interstitial pancreatitis were observed both in animals injected with chromatographed insulin or once crystallized insulin, which can be fractionated into true Sanger insulin, a number of insulin compounds including proinsulin, and many undefined proteins of higher molecular weight. While the occurrence of periductulitis was not dependent on dosage, peri-insulitis was only found with certain dose ranges in both groups. Injections of once crystallized insulin evoked peri-insular infiltrates at a low dosage, injections of chromatographed insulin at a high dosage. The possibility is discussed as to whether or not the peri-insular and peri-ductular infiltrates reflect a cellular immune response induced by fractions of crystalline insulin, which may differ from true Sanger insulin.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Congenital diabetes mellitus ; absence of beta cells ; methylmalonic acidaemia ; mutase deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report on a female neonate with diabetes mellitus and methylmalonic acidaemia, who died at age 16 days. Using immunocytochemistry, electron microscopy and in situ hybridisation, we were unable to demonstrate any insulin cells in the pancreatic islets. Methylmalonic acidaemia was caused by a methylmalonyl coenzyme A mutase apoenzyme defect. The metabolic crisis of the methylmalonic acidaemia aggravated the diabetes and may explain the failure of insulin therapy. Our results suggest that the infant suffered from a congenital absence of beta cells associated with a genetically transmitted mutase apoenzyme defect.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 8 (1972), S. 19-28 
    ISSN: 1432-0428
    Keywords: Mouse pancreatic islets ; β-cells ; stimulation anti-insulin serum ; diabetic syndrome ; enzymehisto-chemical studies ; α-glycerophosphate oxydase ; acid phos-phatase ; glucose-6-phosphate dehydrogenase ; glucose-6-phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On a procédé à l'examen histochimique enzymatique d'îlots de Langerhans sur des souris ayant un syndrome diabétique après injection unique, ou répétée, de sérum anti-insuline, et on les a comparés avec des résultats normaux. Les variations de l'activité des enzymes des cellules-B se sont trouvées en accord avec les résultats histopathologiques de dégranulation importante et de variations hypersécrétoires des cellules-B. L'α-glycérophosphate-oxydase (GPOX) a montré la diminution d'activité la plus sensible et la plus forte. Par contre la diminution de l'activité de la phosphatase acide (ACPase) était moins forte. La glucose-6-phosphatedéshydrogénase (G-6-P-DH) a accusé une activité de même intensité que dans un cas normal. La glucose-6-phosphatase (G-6-Pase) fut le seul enzyme à faire preuve d'une accroissement d'activité. Les activités de la cytochrome-oxydase (CCOX), de la lactico-déshydrogénase (LDH), de la succino-déshydrogénase (SDH), de la phosphatase alcaline (AP), ainsi que de l'adénosine-triphosphatase (ATPase) sont restées sans changement. — Le rôle du cycle du pentose phosphate (enzyme indicateur: G-6-P-DH), du cycle du glycérophosphate (enzyme indicateur: GPOX) et de la phosphorylation du glucose (enzyme indicateur G-6-Pase) est discuté en ce qui concerne le mécanisme de synthèse et de libération de l'insuline.
    Abstract: Zusammenfassung Es wurden enzymhistochemische Untersuchungen an den Langerhansschen Inseln von Mäusen mit einem diabetischen Syndrom nach einmaliger und wiederholter Injektion von Anti-Insulin-Serum durchgeführt und mit Normalbefunden verglichen. Analog zu den pathohistologischen Befunden einer starken Degranulierung und hypersekretorischer Alterationen der B-Zellen fanden sich Aktivitätssteigerungen bei einigen Enzymen im Bereich der Inseln. — Die empfindlichste und stärkste Aktivitätsminderung ließ die α-Glycerophosphatase (GPOX) erkennen. Weniger stark war die Aktivitätsabnahme der sauren Phosphatase (SP). Eine gleichstarke Aktivität wie im Normalfall wies die Glucose-6-Phosphat Dehydrogenase (G-6-P-DH) auf. Als einziges Enzym zeigte die Glucose-6-Phosphatase (G-6-Pase) eine Aktivitätssteigerung. Die Aktivität der Cytochromoxydase (CCOX), Lactat-Dehydrogenase (LDH), Succino-Dehydrogenase (SDH), alkalischen Phosphatase (AP) und Adenosintriphosphatase (ATPase) blieb unverändert. Die Befunde werden im Zusammenhang mit den hypothetischen Beziehungen des Pentosephosphatcyclus (Indikatorenzym: G-6-P-DH), des Glycerophosphatcyclus (Indikatorenzym: GPOX) und der Glucosephosphorylierung (Indikatorenzym: G-6-Pase) zur Insulinsynthese und -Sekretion diskutiert.
    Notes: Summary Islets of Langerhans in white mice with a diabetic syndrome after single and repeated injections of anti-insulin serum were studied by enzymehistochemical methods and compared with controls. Changes in activity of some enzymes were noted in the islet area in accordance with the histopathological findings of severe degranulation and hypersecretory changes of the beta cells. — The α-glycerophosphate oxidase (GPOX) showed the most sensitive and severe decrease of activity whereas the acid phosphatase (ACPase) was only slightly decreased. Compared with the enzyme activity in normal mice, no significant changes of glucose-6-phosphate dehydrogenase (G-6-PD) could be observed. The only enzyme showing an increased activity was the glucose-6-phosphatase (G-6-Pase). The studies of the cytochrome oxidase (CCOX), lactic dehydrogenase (LDH), succinic dehydrogenase (SDH), acid phosphatase (ACPase), alkaline phosphatase (APase) and adenosine triphosphatase (ATPase) revealed no alterations of the enzyme patterns under these experimental conditions. The findings are discussed with regard to the hypothetical relations between the pentose phosphate shunt (indicator enzyme: G-6-PD), the glycerophosphate cycle (indicator enzyme: GPOX) and the phosphorylation of glucose (indicator enzyme: G-6-Pase) to insulin synthesis and release.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 35 (1992), S. 272-276 
    ISSN: 1432-0428
    Keywords: Islet amyloid polypeptide ; fetal pancreas ; immunocytochemistry ; distribution ; age dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Islet amyloid polypeptide is known to localize to the adult human Beta cell. We analysed the immunoreactivity for islet amyloid polypeptide in a series of 29 human fetal pancreata (9–24 weeks of gestation) with respect to age dependency and cellular localization using an antibody raised against synthetic rat islet amyloid polypeptide 12–37. Cells immunoreactive for islet amyloid polypeptide were demonstrated in low numbers from week 13 onwards while insulin positivity was already present at 9 weeks of gestation. In the age group 13–16 gestational weeks, cells positive for insulin were 20-fold more frequent than cells positive for islet amyloid polypeptide. This difference gradually disappeared with age, reaching parity in the adult gland. Double immunostaining demonstrated that all islet amyloid polypeptide immunoreactivity co-localized with insulin. Co-expression of insulin and islet amyloid polypeptide was more frequent in Beta-cell clusters (≥10 cells) than in single Beta cells; islet amyloid polypeptide positivity was present in 58±9% (mean±SEM; n=4) of fetal, 88±9 % (n=3) of neonatal and 100% (n=3) of adult clustered Beta cells, and only 8–18 % of the single Beta cells. The results suggest that the developing fetal Beta cells, dependent on age and localization, differ in their capacity to express detectable amounts of immunoreactive islet amyloid polypeptide. Beta-cell maturation might therefore be associated with islet amyloid polypeptide expression.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Neonatal-STZ rat model ; beta-cell growth ; BrdU labelling index ; immunocytochemistry ; morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Regeneration of neonatal beta cells after subtotal streptozotocin (STZ)-induced destruction is incomplete but nevertheless leads to rapid remission of hyperglycaemia. To study the proliferative and functional capacity of regenerated beta cells in adolescent and adult rats after early beta-cell damage and to determine the time point after birth which is decisive for regeneration, beta-cell growth and metabolic capacity were analysed in rats treated during the neonatal period with STZ (100 Μg/g body weight) and studied over 3 to 20 weeks. Using immunocytochemistry combined with morphometry we found that the regenerated beta cells continue to increase in number till week 6 of life, when they reached values of more than 50% of those of controls. After week 6, the regenerated beta cells had enlarged in size but failed to further increase their number, although their proliferative activity, determined by bromodeoxyuridine (BrdU) pulse labelling, was still higher at 6 and 10 weeks than that of normal rats. The inability of regenerated beta cells to further increase their number coincided with a deterioriation of their function (week 10, male rats; week 20, female rats). When beta cells were destroyed on day 2 or 5 instead of the day of birth, regeneration of beta cells markedly decreased and the rats were already on the threshold of development of glucose intolerance at 3 weeks of age. We conclude that the partially regenerated beta-cell population in rats treated with STZ on the day of birth ceases to grow 10 to 20 weeks later. This growth arrest may be due to the sustained functional demand to which these beta cells are exposed in order to compensate for their reduced number. Beta-cell capacity for regeneration declines rapidly during the first days of life.
    Type of Medium: Electronic Resource
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