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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 479-484 
    ISSN: 1432-0428
    Keywords: Pyruvate dehydrogenase complex ; branched chain ketoacid dehydrogenase complex ; diabetes ; starvation ; low protein diets ; activator protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Activity of the pyruvate dehydrogenase complex determines the rate of glucose oxidation in animals including man. The complex is regulated by reversible phosphorylation, phosphorylation resulting in inactivation. Activity is therefore dependent upon the activities of pyruvate dehydrogenase kinase and phosphatase. Activity of the complex is reduced in diabetes and starvation as a result of insulin deficiency. The mechanism involves activation of pyruvate dehydrogenase kinase by short-term effects of products of fatty acid oxidation and by longer term effects involving specific protein synthesis; in hepatocytes the signals may include lipid fuels and glucagon. Activity of the branched chain ketoacid dehydrogenase complex determines the rate of degradation of branched chain aminoacids which is adjusted according to dietary supply The complex is regulated by reversible phosphorylation, phosphorylation being inactivating. In liver and kidney, but not in muscles a protein activator (free El component) may reactivate phosphorylated complex without dephosphorylation and facilitate hepatic oxidation of branched chain ketoacids. Metabolic adjustments induced by diet and diabetes include loss of activator protein, loss of total complex activity in liver but not muscles, and enhanced inactivation by phosphorylation in liver.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 36 (1993), S. 1215-1217 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 36 (1993), S. 269-275 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Urinary conjugated glucose ; urinary glucosyl/galactosyl ratio ; Type 1 diabetes ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Urine contains non-dialysable conjugates of glucose and galactose from which the free sugars are released by acid hydrolysis. In 14 non-diabetic subjects the 24-h outputs (mean±SEM) were 25±3 umol/24 h (glucose) and 109±15 μmol/l (galactose). In collections from 23 diabetic patients output of conjugated glucose was increased to 177±96 μmol/24 h but conjugated galactose was unchanged (119±10 μmol/24 h). The concentration ratio of glucosyl/galactosyl allows relative 24-h outputs of conjugated glucose to be estimated on random samples. The ratio (mean±SEM) was 0.24±0.01 in 27 normal men and 0.37±0.04 in 30 normal women. The mean ratio was increased to 0.72±0.20 in 56 male and to 0.51±0.07 in 17 female diabetic patients. In individual diabetic patients, the ratio was increased significantly in 28 out of 56 men and in 5 out of 30 women. In male diabetic patients the ratio was increased in 17 out of 23 Type 1 (insulin-dependent) but in only 3 out of 15 Type 2 (non-insulin-dependent) diabetic patients. There was no correlation between the glucosyl/galactosyl ratio and patient age, known duration of diabetes, or urinary excretion of free glucose or protein. Urine samples showing increased glucosyl/galactosyl ratios did not yield bacteria on culture and were negative for Candida albicans cell-wall mannan antigen. It is concluded that 80% of male Type 1 diabetic patients show increased urinary excretion of non-dialysable conjugated glucose. In women, there is much greater variation in non-diabetic subjects which may obscure an increased excretion in diabetic patients.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. S155 
    ISSN: 1432-0428
    Keywords: Glucose fatty acid cycle ; glucose oxidation ; diabetes mellitus ; starvation ; pyruvate dehydrogenase complex ; pyruvate dehydrogenase kinase ; pyruvate dehydrogenase phosphatase ; fatty acids ; cyclic AMP ; cultured hepatocytes ; cultured cardiac myocytes ; soleus muscle ; insulin action ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Glucose Fatty Acid Cycle as formulated 30 years ago and reviewed in the Minkowski lecture in 1966 described short term effects of fatty acids (minutes) to decrease uptake, glycolysis and oxidation of glucose in heart and skeletal muscles. Such short term effects have since been extended to include inhibition of glucose uptake and glycolysis and stimulation of gluconeogenesis in liver and these effects have also been convincingly demonstrated in man in vivo. More recently a longer term effect of fatty acid metabolism to decrease glucose oxidation (hours) has been shown in heart and skeletal muscle and liver. This effect increases the specific activity of pyruvate dehydrogenase kinase, which in turn results in enhanced phosphorylation and inactivation of the pyruvate dehydrogenase complex. Activity of the pyruvate dehydrogenase complex is the major determinant of glucose oxidation rate. It seems likely that longer term effects of fatty acids on this and other aspects of glucose metabolism could be important in the development of insulin resistance in diabetes mellitus in man.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Quantitative electron microscopy ; rabbit pancreas ; β-cells ; In vitro ; stimulation glucose tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On a comparé l'aspect au microscope électronique des cellules bêta de pancréas de lapin prélevésin vivo et après incubationin vitro, et on a étudié les effets, sur la cytomorphologie de la cellule bêta, de la stimulation de la libération d'insulinein vitro par un taux élevé de glucose et par le tolbutamide. Une partie des cellules bêta conservait sa structure normale au cours de l'incubationin vitro; ceci variait dans les différents échantillons de 35 à 100 pour cent. La cause de cette variation n'était pas apparente, mais elle n'était pas influencée par la durée de l'incubation, ni par la concentration du milieu en glucose, ni par le tolbutamide. On a fait des mesures quantitatives de la proportion de profils de cellules bêta, présentant une distribution marginale des granules, du nombre de contacts entre les membranes des sacs granulaires et la membrane plasmatique, du nombre de sacs granulaires présentant des perforations, de la densité de population des granules spécifiques de sécrétion, des lysosomes et des corps autophagiques, et on a fait des estimations de l'étendue de l'appareil de Golgi dans les coupes transversales. On n'a pas observé de modifications constantes dans ces paramètres après stimulation de la libération d'insuline par le glucose ou le tolbutamide. Dans aucun des spécimens examinés il n'y avait de signe de continuité entre l'intérieur d'un sac granulaire et l'extérieur d'une cellule bêta. Des calculs basés sur le taux de libération d'insuline et sur le contenu en insuline du pancréas, indiquent qu'il y a peu de chance de visualiser l'extrusion d'un granule au microscope électronique. L'importance de ces résultats en relation avec la théorie d'émiocytose de la sécrétion d'insuline (Lacy andHartroft) est discutée.
    Abstract: Zusammenfassung Das elektronenoptische Bild von β-Zellen ausin vivo entnommenem Kaninchenpankreas wurde vor und nachin vitro Inkubation verglichen und die Auswirkungen der invitro durch Glucose und Tolbutamid herbeigeführten Insulinfreisetzung auf die β-Zell-Zytomorphologie untersucht. Ein Teil der β-Zellen behielt auch nachin vitro Inkubation seine normale Struktur; dieser Anteil schwankte in den verschiedenen Ansätzen zwischen 35 und 100%. Die Ursache dieser Schwankungen ließ sich nicht nachweisen. Die Inkubationsdauer und die Glucose- oder Tolbutamidkonzentration im Medium hatten keinen Einfluß darauf. Quantitativ bestimmt wurden: Der Anteil der β-Zellprofile, die eine randständige Granulaverteilung aufwiesen; die Anzahl der Kontakte zwischen Granula- und Plasmamembran; die Anzahl der Granula, die Perforationen aufwiesen; die Bevölkerungsdichte spezifischer Sekretionsgranula und die Zahl der Lysosomen und Autophagen. Ferner wurde die Ausprägung des Golgi-Apparates in den einzelnen Schnitten geschätzt. Nach Anregung der Insulinfreisetzung durch Glucose oder Tolbutamid wurden keine konstanten Änderungen dieser Parameter beobachtet. In keinem der untersuchten Präparate ließ sich eine Verbindung zwischen dem Inneren eines Granula-Sackes und der Umgebung der Zelle nachweisen. Berechnungen, die sich auf die Insulinfreisetzungsrate und auf den Insulingehalt des Pankreas stützen, ergeben allerdings nur eine geringe Wahrscheinlichkeit dafür, daß sich ein Granulaaustritt elektronenmikroskopisch darstellen läßt. Die Bedeutung dieser Ergebnisse in Bezug auf die Emiozytose-Theorie der Insulinfreisetzung (Lacy undHartroft) wird besprochen.
    Notes: Summary The electron microscopic appearances of rabbit pancreas β-cells takenin vivo and afterin vitro incubation have been compared and the effects of high glucose and tolbutamide stimulation of insulin releasein vitro on β-cell cytomorphology investigated. Normal structure was maintained onin vitro incubation in a proportion of β-cells; this varied in different samples from 35–100 per cent. The cause of this variation was not apparent but it was not influenced by the time of incubation, medium glucose concentration or tolbutamide. Quantitative measurements have been made of the proportion of β-cell profiles showing marginal distribution of granules, of the number of contacts between granule sac membranes and the plasma membrane, of the number of granule sacs showing perforations, of the population density of specific secretion granules, lysosomes and autophagic bodies, and estimates have been made of the extent of the Golgi apparatus in cross section. No consistent change in these parameters was observed following stimulation of insulin release with glucose or tolbutamide. There was no evidence in any of the specimens examined of continuity between the interior of a granule sac and the outside of a β-cell. Calculations based on the rate of release of insulin and the insulin content of the pancreas indicate that the chance of visualising granule extrusion by electron microscopy is small. The significance of these results in relation to the emiocytosis theory of insulin release (Lacy andHartroft) is discussed.
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