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  • 1
    Electronic Resource
    Electronic Resource
    Soluble, fatty acid acylated insulins bind to albumin and show protracted action in pigs (1996)
    Springer
    Diabetologia 39 (1996), S. 281-288 
    Details
    ISSN: 1432-0428
    Keywords: Insulin analogues ; albumin binding ; prolonged action ; basal insulin ; fatty acids ; tetradecanoic acid ; myristic acid ; lysineB29 ; acylation ; receptor affinity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have synthesized insulins acylated by fatty acids in the ε-amino group of LysB29. Soluble preparations can be made in the usual concentration of 600 nmol/ml (100 IU/ml) at neutral pH. The time for 50% disappearance after subcutaneous injection of the corresponding TyrA14(125I)-labelled insulins in pigs correlated with the affinity for binding to albumin (r=0.97), suggesting that the mechanism of prolonged disappearance is binding to albumin in subcutis. Most protracted was LysB29-tetradecanoyl des-(B30) insulin. The time for 50% disappearance was 14.3±2.2 h, significantly longer than that of Neutral Protamine Hagedorn (NPH) insulin, 10.5±4.3 h (p〈0.001), and with less inter-pig variation (p〈0.001). Intravenous bolus injections of LysB29-tetradecanoyl des-(B30) human insulin showed a protracted blood glucose lowering effect compared to that of human insulin. The relative affinity of LysB29-tetradecanoyl des-(B30) insulin to the insulin receptor is 46%. In a 24-h glucose clamp study in pigs the total glucose consumptions for LysB29-tetradecanoyl des-(B30) insulin and NPH were not significantly different (p=0.88), whereas the times when 50% of the total glucose had been infused were significantly different, 7.9±1.0 h and 6.2±1.3 h, respectively (p〈0.04). The glucose disposal curve caused by LysB29-tetradecanoyl des-(B30) insulin was more steady than that caused by NPH, without the pronounced peak at 3 h. Unlike the crystalline insulins, the soluble LysB29-tetradecanoyl des-(B30) insulin does not elicit invasion of macrophages at the site of injection. Thus, LysB29-tetradecanoyl des-(B30) insulin might be suitable for providing basal insulin in the treatment of diabetes mellitus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418343
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Soluble, fatty acid acylated insulins bind to albumin and show protracted action in pigs (1996)
    Springer
    Diabetologia 39 (1996), S. 281-288 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin analogues ; albumin binding ; prolonged action ; basal insulin ; fatty acids ; tetradecanoic acid ; myristic acid ; lysineB29 ; acylation ; receptor affinity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have synthesized insulins acylated by fatty acids in the ɛ-amino group of LysB29. Soluble preparations can be made in the usual concentration of 600 nmol/ml (100 IU/ml) at neutral pH. The time for 50 % disappearance after subcutaneous injection of the corresponding TyrA14(125I)-labelled insulins in pigs correlated with the affinity for binding to albumin (r = 0.97), suggesting that the mechanism of prolonged disappearance is binding to albumin in subcutis. Most protracted was LysB29-tetradecanoyl des-(B30) insulin. The time for 50 % disappearance was 14.3 ± 2.2 h, significantly longer than that of Neutral Protamine Hagedorn (NPH) insulin, 10.5 ± 4.3 h (p 〈 0.001), and with less inter-pig variation (p 〈 0.001). Intravenous bolus injections of LysB29-tetradecanoyl des-(B30) human insulin showed a protracted blood glucose lowering effect compared to that of human insulin. The relative affinity of LysB29-tetradecanoyl des-(B30) insulin to the insulin receptor is 46 %. In a 24-h glucose clamp study in pigs the total glucose consumptions for LysB29-tetradecanoyl des-(B30) insulin and NPH were not significantly different (p = 0.88), whereas the times when 50 % of the total glucose had been infused were significantly different, 7.9 ± 1.0 h and 6.2 ± 1.3 h, respectively (p 〈 0.04). The glucose disposal curve caused by LysB29-tetradecanoyl des-(B30) insulin was more steady than that caused by NPH, without the pronounced peak at 3 h. Unlike the crystalline insulins, the soluble LysB29-tetradecanoyl des-(B30) insulin does not elicit invasion of macrophages at the site of injection. Thus, LysB29-tetradecanoyl des-(B30) insulin might be suitable for providing basal insulin in the treatment of diabetes mellitus. [Diabetologia (1996) 39: 281–288]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418343
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Regulation of GAD expression in rat pancreatic islets and brain by γ-vinyl-GABA and glucose (1998)
    Springer
    Diabetologia 41 (1998), S. 530-535 
    Details
    ISSN: 1432-0428
    Keywords: Keywords GAD ; GABA ; GABA-transaminase ; GVG ; pancreas ; brain ; rat ; islet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM), but little is known about its regulation and function in islet cells. We investigated the effects of the GABA-transaminase inhibitor γ-vinyl-GABA (GVG) on GAD expression in rat islets and brain in vitro and in vivo. In islets incubated in high glucose culture medium there was an increase in GAD activity, GAD65 and GAD67 protein levels compared to low-glucose conditions; however, even in high glucose, GVG still significantly suppressed GAD activity and GAD67 expression. Our observations suggest that glucose and GVG act on GAD in islets through different mechanisms. Quantitative immunohistochemistry of pancreatic sections from rats treated with GVG in vivo using novel monoclonal antibodies specific for GAD65 and GAD67, showed a decrease in GAD67 expression (p 〈 0.005) relative to untreated rats. The effects of GVG on rat pancreatic islets were very similar to those observed in brain of rats treated with GVG in vivo. In homogenates of cerebral tissue from GVG treated rats containing both membrane-bound and soluble protein GAD67 levels were significantly decreased while GAD65 levels were not significantly changed compared to untreated rats. In contrast, in homogenates of cerebral tissues containing only soluble cytosolic protein, GVG-treatment was also significantly found to decrease GAD65 levels. Taken together, these results suggest that GVG potentially could be of use to decrease GAD expression in islet cells and consequently to deviate/inhibit the autoimmune response against the beta cells seen in IDDM. [Diabetologia (1998) 41: 530–535]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050942
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Specific antagonism by dopamine inhibitors of items of amphetamine induced aggressive behaviour (1972)
    Springer
    Psychopharmacology 24 (1972), S. 485-495 
    Details
    ISSN: 1432-2072
    Keywords: Aggression ; Amphetamine ; Dopamine ; Mice ; Stereotypy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract d-Amphetamine in a dose of 15 mg/kg elicits both aggressive activities and stereotyped sniffing, licking and biting of the cage in mice. A selective inhibition of the aggressive activities (without general sedation of the mice) was obtained by small doses of the neuroleptics spiramide and trifluperazine, indicating that this behaviour was mediated by increased activity of dopamine in the brain. This indication was supported by experiments with noradrenaline blocking agents and inhibitors of the synthesis of dopamine and noradrenaline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00423439
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Dye standards, Part I: terminology and general principles (1992)
    Springer
    Journal of molecular histology 24 (1992), S. 217-219 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01046791
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    Paper (German National Licenses)
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