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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
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Enzymatic determination of 1-14C-glucose in pig plasma (1989)
    Springer
    Diabetologia 32 (1989), S. 660-662 
    Details
    ISSN: 1432-0428
    Keywords: 1-14C-glucose ; enzymatic assay ; glucose tracers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A simple and cheap one-step enzymatic method has been developed for the determination of 1-14C-glucose in plasma. C-1 of glucose is cleaved off as CO2 by treatment with hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconic dehydrogenase. True 1-14C-glucose activity is then calculated as the difference between total radioactivity and radioactivity remaining after enzyme treatment and evaporation. The reaction is shown to be quantitative and specific, thus eliminating both labelled metabolites and label recycled to other positions in glucose. Two different types of pig experiments show that 1-14C-glucose, when determined by this method, is as irreversible a tracer as the commonly used 3-3H-glucose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00274253
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    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
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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