Zełobowska Katarzyna, Gumprecht Janusz, Grzeszczak Władysław
Department of Internal Medicine, Diabetology, and Nephrology, Medical University of Silesia, Zabrze.
Endokrynol Pol. 2009 Jan-Feb;60(1):34-9.
The goal of diabetes mellitus treatment is to maintain long-term near-normoglycaemia to prevent the onset or progression of long-term complications. In order to achieve tight glycaemic control and improve the quality of life for diabetic patients, a number of novel insulin preparations, insulin analogues, have been constructed thanks to recombinant DNA technologies and advanced protein chemistry. Because structurally modified insulins may differ from human insulin not only in metabolic but also in mitogenic potencies there were concerns raised about the possibility of increased insulin analogue proliferative action or tumourigenesis. In vitro and in vivo studies on insulin analogues in comparison to endogenous insulin have been performed to closely monitor the insulin analogue action profiles. Insulin glargine was the only one presenting a significant increase in affinity to insulin-like growth factor type 1 (IGF-1) receptor. However, there was controversy regarding the safety of insulin glargine use because of its potential risk of mitogenicity but it proved to be true only for human osteosarcoma cells Saos/B10. Outcomes of the studies performed on lines other than cancer cells and on animals did not present any increased mitogenic activity nor mitogenic potency of insulin glargine in comparison to human insulin.
糖尿病治疗的目标是维持长期血糖接近正常水平,以预防长期并发症的发生或进展。为了实现严格的血糖控制并改善糖尿病患者的生活质量,借助重组DNA技术和先进的蛋白质化学,已构建了多种新型胰岛素制剂,即胰岛素类似物。由于结构修饰的胰岛素不仅在代谢方面,而且在促有丝分裂能力方面可能与人体胰岛素不同,因此人们对胰岛素类似物增殖作用增强或发生肿瘤的可能性表示担忧。已开展了关于胰岛素类似物与内源性胰岛素对比的体外和体内研究,以密切监测胰岛素类似物的作用谱。甘精胰岛素是唯一一种与1型胰岛素样生长因子(IGF-1)受体亲和力显著增加的胰岛素。然而,由于甘精胰岛素存在潜在的促有丝分裂风险,其使用安全性存在争议,但这仅在人骨肉瘤细胞Saos/B10中得到证实。与人体胰岛素相比,在癌细胞系以外的细胞系和动物上进行的研究结果并未显示甘精胰岛素有任何促有丝分裂活性增加或促有丝分裂能力增强的情况。