Chytry V, Letourneur D, Baudys M, Jozefonvicz J
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic Prague, Czech Republic.
J Biomed Mater Res. 1996 Jun;31(2):265-72. doi: 10.1002/(SICI)1097-4636(199606)31:2<265::AID-JBM14>3.0.CO;2-K.
The hypothesis that an elevated plasma insulin level contributes to an increase in coronary heart disease has led to studies of the mitogenic effect of native insulin and its conjugates on smooth muscle cells (SMC). In this study, insulin was covalently attached to two water-soluble polymers containing N-(2-hydroxypropyl)methacrylamide using the mixed anhydride method. The first polymer was a copolymer of N-(2-hydroxypropyl)methacrylamide and N-methacryloyldiglycine. The second one was a terpolymer of two of the above-given monomers and R-(-)-1-methyl-2-methacryloylamidoethyl 2-acetamido-2-deoxy-beta-D-glucopyranoside. Insulin conjugates were isolated and characterized, and the mitogenic effect on SMC was investigated. The results showed that only conjugates of insulin and terpolymers bearing pendant N-acetyl-glucosamine groups do not have a mitogenic effect on SMC while maintaining the hypoglycemic activity of insulin. This finding suggests that some inter- or intramolecular interactions of coupled insulin with the sugar moiety(ies) attached to the polymer backbone contribute to the observed effects.
血浆胰岛素水平升高会导致冠心病增加这一假说引发了对天然胰岛素及其缀合物对平滑肌细胞（SMC）的促有丝分裂作用的研究。在本研究中，使用混合酸酐法将胰岛素共价连接到两种含有N-（2-羟丙基）甲基丙烯酰胺的水溶性聚合物上。第一种聚合物是N-（2-羟丙基）甲基丙烯酰胺和N-甲基丙烯酰基二甘氨酸的共聚物。第二种是上述两种单体与R-（-）-1-甲基-2-甲基丙烯酰氨基乙基2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖苷的三元共聚物。分离并表征了胰岛素缀合物，并研究了其对SMC的促有丝分裂作用。结果表明，只有胰岛素与带有N-乙酰氨基葡萄糖侧基的三元共聚物的缀合物对SMC没有促有丝分裂作用，同时保持了胰岛素的降血糖活性。这一发现表明，偶联胰岛素与连接在聚合物主链上的糖部分之间的一些分子间或分子内相互作用导致了观察到的效应。
