| Autor: |
Markussen, J., Havelund, S., Kurtzhals, P., Andersen, A., Halstrøm, J., Hasselager, E., Larsen, U., Ribel, U., Schäffer, L., Vad, K., Jonassen, I. |
| Zdroj: |
Diabetologia; Mar1996, Vol. 39 Issue 3, p281-288, 8p |
| Abstrakt: |
We have synthesized insulins acylated by fatty acids in the ε-amino group of Lys. 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 Tyr(I)-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 Lys-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 Lys-tetradecanoyl des-(B30) human insulin showed a protracted blood glucose lowering effect compared to that of human insulin. The relative affinity of Lys-tetradecanoyl des-(B30) insulin to the insulin receptor is 46%. In a 24-h glucose clamp study in pigs the total glucose consumptions for Lys-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 Lys-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 Lys-tetradecanoyl des-(B30) insulin does not elicit invasion of macrophages at the site of injection. Thus, Lys-tetradecanoyl des-(B30) insulin might be suitable for providing basal insulin in the treatment of diabetes mellitus. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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