ACTION PROFILE OF THE RAPID ACTING INSULIN ANALOG - HUMAN INSULIN B28ASP

被引:86
作者
HEINEMANN, L
HEISE, T
JORGENSEN, LN
STARKE, AAR
机构
[1] Department of Nutrition and Metabolism (Who Collaborating Centre for Diabetes), Heinrich-Heine-University of Düsseldo, Düsseldorf
[2] Novo Nordisk A/S, Bagsvaerd
关键词
INSULIN ANALOGS; PHARMACOKINETICS; PHARMACODYNAMICS; TIME ACTION PROFILES;
D O I
10.1111/j.1464-5491.1993.tb00116.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The time-action profile of the human insulin analogue B28Asp, which displays faster absorption rates from subcutaneous tissue compared to soluble human insulin, was studied under euglycaemic glucose clamp conditions (blood glucose 5.0 mmol l-1) in 14 healthy male volunteers. Subcutaneous injection of 0.15 U kg-1 body weight (range 9.5-14.3 U) of the insulin analogue or soluble human insulin resulted in half-maximal glucose infusion rates (after subtraction of mean baseline glucose infusion rates) that were reached significantly earlier after injection of B28Asp (45 +/- 11 (SD) min) as compared to human insulin (58 +/- 25 min, p < 0.05). Forty-five and 60 min after injection of human insulin, glucose infusion rates had increased by 3.4 +/- 1.8 and 4.8 +/- 2.3 mg min-1 kg-1 above baseline glucose infusion rates, reflecting 30 +/- 15 and 42 +/- 17 % of maximal action of 10.6 +/- 2.7 mg min-1 kg-1. Following the injection of B28Asp, glucose infusion rates increased by 6.3 +/- 2.7 after 45 min and by 7.9 +/- 2.8 mg min-1 kg-1 after 60 min above baseline glucose infusion rates, reflecting 64 +/- 28 % and 81 +/- 26 % of maximal action of human soluble insulin (p < 0.001). Peak glucose infusion rates after injection of B28Asp were significantly higher and were reached earlier than after subcutaneous injection of soluble human insulin (p < 0.05 and p < 0.001). The human insulin analogue B28Asp showed a significantly faster onset of action as compared to soluble human insulin.
引用
收藏
页码:535 / 539
页数:5
相关论文
共 10 条
[1]  
Bornfeldt KE, Gidolf RA, Wasteson A., Lake M., Skottner A., Arnquist HJ., Binding and biological effects of insulin, insulin analogues and insulin‐like growth factors in rat aortic smooth muscle cells. Comparison of maximal growth promoting activities, Diabetologia, 34, pp. 307-313, (1991)
[2]  
Jorgensen LN, Dideriksen LH, Drejer K., Carcinogenic effect of the human insulin analogue B10Asp in female rats, Diabetologia, 35, (1992)
[3]  
Brange J., Owens DR, Kang S., Volund, Monomeric insulins and their experimental and clinical implications, Diabetes Care, 13, pp. 923-954, (1990)
[4]  
Volund, Brange J., Drejer K., Jensen I., Markussen J., Ribel U., Et al., In vitro and in vivo potency of insulin analogues designed for clinical use, Diabetic Medicine, 8, pp. 839-847, (1991)
[5]  
Drejer K., Kruse V., Larsen UD, Hougaard P., Soren B., Gammeltoft S., Receptor binding and tyrosine kinase activation by insulin analogues with extreme affinities studied in human hepatoma HepG2 cells, Diabetes, 40, pp. 1488-1495, (1991)
[6]  
Heinemann L., Starke AAR, Heding L., Jensen I., Berger M., Action profiles of fast onset insulin analogues, Diabetologia, 33, pp. 384-386, (1990)
[7]  
Starke AAR, Heinemann L., Hohmann A., Berger M., The action profiles of human NPH insulin preparations, Diabetic Med, 6, pp. 239-244, (1989)
[8]  
Kang S., Creagh FM, Peters JR, Brange J., Volund, Owens DR., Comparison of subcutaneous soluble human insulin and insulin analogues (Asp<sup>B9</sup> Glu<sup>B27</sup>
[9]  
Asp<sup>B10</sup>
[10]  
Asp<sup>B28</sup>) on meal‐related plasma glucose excursions in type 1 diabetic subjects, Diabetes Care, 14, pp. 571-577, (1991)