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РЖ ВИНИТИ 34 (BI48) 97.11-04Т2.252

Acylation of human insulin with palmitic acid extends the time action of human insulin in diabetic dogs [Text] / Sharon R. Myers [et al.] // Diabetes. - 1997. - Vol. 46, N 4. - P637-642 . - ISSN 0012-1797
Перевод заглавия: Ацилирование инсулина человека пальмитиновой кислотой увеличивает продолжительность действия инсулина у собак с диабетом
Аннотация: To test whether the binding of insulin to an endogenous serum protein can be used to extend the time action of insulin, human insulin was acylated at the epsilonamino group of Lys(B[29]) with palmitic acid to promote binding to serum albumin. Size-exclusion chromatography was used to demonstrate specific binding of the resulting analog, [N{'эпсилон'}-palmitoyl Lys(B[29])] human insulin, to serum albumin in vitro, and the time action and activity of the analog were determined in vivo using overnight-fasted, insulin-withdrawn diabetic dogs. In the diabetic animal model, the duration of action of [N{'эпсилон'}-palmitoyl Lys(B[29])] human insulin administered intravenously was nearly twice that of unmodified human insulin, and the plasma half-life was nearly sevenfold that of the unmodified protein. Administered subcutaneously, [N{'эпсилон'}-palmitoyl Lys(B[29])] human insulin had a longer duration of action; a flatter more basal plasma insulin profile; and a lower intersubject variability of response than the intermediate-acting insulin suspension Humulin L (Lilly, Indianapolis, IN). These studies support the concept that modification of insulin to promote binding to an existing serum protein can be used to extend the time action of human insulin. In addition, the time action, pattern, and decreased variability of response to [N{'эпсилон'}-palmitoyl Lys(B[29])] human insulin support the development and further testing of this soluble insulin analog as a basal insulin to increase the safety of intensive insulin therapy. Библ. 31

ГРНТИ	34.45.21

ВИНИТИ 341.45.21.65.33
Рубрики: ИНСУЛИН
АЦИЛИРОВАННЫЙ ИНСУЛИН ЧЕЛОВЕКА
ДИАБЕТ
ПРОДОЛЖИТЕЛЬНОСТЬ ДЕЙСТВИЯ
СОБАКИ

Доп.точки доступа:
Myers, Sharon R.; Yakubu-Madus, Fatima E.; Johnson, William T.; Baker, James E.; Cusick, Tania S.; Williams, Valerie K.; Tinsley, Frank C.; Kriauciunas, Aidas; Manetta, Joseph; Chen, Victor J.

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