Hori R, Komada F, Iwakawa S, Seino Y, Okumura K
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Pharm Res. 1989 Sep;6(9):813-6. doi: 10.1023/a:1015987800808.
The present study was undertaken to develop an agent that stabilizes insulin injected subcutaneously. 125I-Porcine insulin with 0.2 U/kg unlabeled porcine insulin was subcutaneously injected with or without collagen in the rat under the depilated skin of the back. At various times, the radioactivity in subcutaneous tissue was assayed for insulin and its metabolites by gel filtration. The degradation and absorption rate constants of insulin at the subcutaneous injection site were estimated according to a one-compartment model. The degradation rate constant of insulin in the presence of collagen at the injection site was less than half of the control rate. The inhibition was confirmed by increases in the immunoreactive insulin plasma levels and the hypoglycemic effect in rats and healthy volunteers. We postulate that collagen prevents insulin from being degraded by inhibiting proteolytic enzymes, mainly collagenase-like peptidase, in subcutaneous tissue.
本研究旨在开发一种能稳定皮下注射胰岛素的制剂。将含0.2 U/kg未标记猪胰岛素的125I-猪胰岛素，在大鼠背部脱毛皮肤下，皮下注射，注射时分别添加或不添加胶原蛋白。在不同时间，通过凝胶过滤法测定皮下组织中胰岛素及其代谢产物的放射性。根据单室模型估算皮下注射部位胰岛素的降解和吸收速率常数。注射部位存在胶原蛋白时，胰岛素的降解速率常数不到对照速率的一半。通过大鼠和健康志愿者血浆中免疫反应性胰岛素水平的升高以及降血糖作用，证实了这种抑制作用。我们推测，胶原蛋白通过抑制皮下组织中的蛋白水解酶（主要是类胶原酶肽酶）来防止胰岛素降解。
