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  • 1
    ISSN: 1432-5233
    Keywords: Electron microscopy ; Glibenclamide ; Glucose oxidation ; Insulin biosynthesis ; Insulin secretion ; Islets of Langerhans ; Mitochondria ; Morphometry ; Tissue culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to evaluate long-term effects of sulphonylureas on pancreatic islet structure and function, isolated mouse islets were maintained in tissue culture for one week at various glucose concentrations, and in the absence or presence of glibenclamide. When the islets were cultured at 3.3 or 5.5 mmol/1, but not at 16.7 mmol/1 glucose, it was found that the drug stimulated insulin secretion into the culture medium during the initial 3 days of culture. During the remainder of the culture period no such enhancement of secretion was demonstrated. Insulin release due to glibenclamide apparently resulted in rapid depletion of intracellular insulin stores. The finding of an enlarged B-cell Golgi apparatus in the drug-treated islets was probably associated with granule discharge. The failure of glibenclamide to promote insulin secretion during the whole culture period could reflect the adverse effects of the drug on islet insulin biosynthesis as indicated by short-term experiments performed after culture. Similar experiments showed that the impaired insulin biosynthesis could not be restored by withdrawal of the drug from the culture medium for 3 days. Furthermore, the capacity for insulin release in response to an acute glucose challenge at the end of the culture period, was abolished by culture in the presence of glibenclamide. The drug effects on insulin biosynthesis and intracellular insulin stores, which were most pronounced at 5.5 mmol/1 glucose, possibly resulted from changes in B-cell metabolism as suggested by the diminished islet glucose-oxidation rate. The spatial characteristics of islet mitochondria indicated that these changes might involve an adaptation to substrates other than glucose. In conclusion, our findings suggest that sulphonylureas have an insulinotropic effect, which is however transient. Indeed, it rather seems as if long-term exposure of islet B-cells to sulphonylureasin vitro were accompanied by functional deficiency.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 241 (1995), S. 255-267 
    ISSN: 0003-276X
    Keywords: Rat ; Diabetic pregnancy ; Embryonic dysmorphogenesis ; Neuroepithelium ; Blood cells ; Mitochondria ; High-amplitude mitochondrial swelling ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Background: Previous studies in vivo and in vitro have suggeted that the oxidative metabolism of the embryo may have a role in the treatogenicity of diabetic pregnancy. In particular, the production of reactive oxygen species by the embroyonic mitochondiria has been implicated in the teratological process. The induction of congenital malformations by the diabetic milieu occurs during the early embryonic development. The present study aimed to estimate the role of the embryonic mitochondria in the teratological process of diabetic pregnancy by studying mitochondrial morphology in the embryos exposed to a diabetic environment in vivo or in vitro during early organogenesis and late fetal development.Methods: For studies in vivo embryos of control or streptozotocin-dia-betic rats were taken at gestational days 9-11 and sujected to light and electron microscopical analysis. The brain, heart, and liver of day-15 fetuses were also observed. For studies in vitro day-9 embryos of normal rats were cultured in a whole-embryo culture system for 48 hours. The culture media were supplied with high conectration of diabetes-related substrates and metabolites, and their effect on structure of embryonic neuropeithelial cells determined.Results: The light microscopoical observations demonstrated numberous cytoplasmic vaculoes in the ectoderm of day-9 embryos and the neuroepithelium and blood cells of day-10 and day-11 embryos of diabetic rats. Ultrastructuraily, these vacuoles were found to be mitochondria undergoing large-amplitude swelling with loss of matrix density and disturbed cristae. In contrast, no Mitochondrial differences were found in the brain, heart, and liver, when day-15 fetuses from normal and diabeic rats were compared. Ultrastructural analysis of day-9 embryos cultured for 48 hours in the presnce of high conectrations of D-Glucose, pyruvate, β-hydroxybutyrate, and α-ketoisocaproate also showed high-amplitude mitochondrial swelling in the neuroepithelium. The motochondrial swelling was, however, not found in embryos cultured in a high conectration of L-glucose, excluding simple osmotic effects of the diabetes-related substrated and metabolites.Conclusions: The mitochondrial morphological changes appeared in embryos subjected to a diabetic environment during a time period when the congenital malformations in diabetic pregnancy are induced. The results support the notion that embryonic mitochondria are involved in the teratological process of diabetic pregnancy. © 1995 Wiley-Liss, inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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