In this study, we developed a subcutaneous insulin-releasing device consisting of a disk-shaped capsule and drug formulation comprised of poly(ethylene glycol) dimethacrylates, then evaluated its efficacy on retinal function in streptozotocin (STZ)-induced diabetic rats. In vitro release studies showed that recombinant human insulin was released with a constant rate for more than 30 days. The device was able to maintain a basal level of blood glucose in diabetic rats for a prolonged period of more than 30 days, simultaneously preventing a decrease in body weight. For assessing the pharmacological effect of the device on retinal function in diabetic rats, electroretinograms were conducted for 12 weeks. The reduction in amplitude and delay in implicit time were attenuated by the device during the initial 4 weeks of application. The increase in gene expression of protein kinase C (PKC)-γ and caspase-3 in the diabetic retina was also attenuated by the device. Immunohistochemistry showed that the increase in glial fibrillary acidic protein expression in the diabetic retina was attenuated by the device. Histological evaluation of subcutaneous tissue around the device showed the biocompatibility of the device. In conclusion, the insulin-releasing device attenuated the reduction of retinal function in STZ-induced diabetic conditions for 4 weeks and the efficacy of the device might be partially related to PKC signaling in the retina. The long-term ability to control the blood glucose level might help to reduce the daily frequency of insulin injections.

在这项研究中，我们开发了一种由盘状胶囊和由聚二甲基丙烯酸乙二醇酯组成的药物制剂组成的皮下胰岛素释放装置，然后评估其对链脲佐菌素（STZ）诱导的糖尿病大鼠视网膜功能的功效。体外释放研究表明重组人胰岛素以恒定速率释放超过30天。该设备能够在糖尿病大鼠中维持超过30天的基本血糖水平，同时防止体重下降。为了评估该装置对糖尿病大鼠视网膜功能的药理作用，进行了12周的视网膜电图检查。在应用的最初4周内，该设备减弱了幅度的减小和隐式时间的延迟。该设备还减弱了糖尿病视网膜中蛋白激酶C（PKC）-γ和caspase-3的基因表达增加。免疫组织化学显示，糖尿病视网膜中胶质纤维酸性蛋白表达的增加被该装置减弱。装置周围的皮下组织的组织学评估显示了装置的生物相容性。总之，胰岛素释放装置可减轻STZ诱导的糖尿病患者视网膜功能的降低达4周，并且该装置的功效可能与视网膜中PKC信号传导部分相关。控制血糖水平的长期能力可能有助于减少每天注射胰岛素的频率。免疫组织化学显示，糖尿病视网膜中胶质纤维酸性蛋白表达的增加被该装置减弱。装置周围的皮下组织的组织学评估显示了装置的生物相容性。总之，胰岛素释放装置可减轻STZ诱导的糖尿病患者视网膜功能的降低达4周，并且该装置的功效可能与视网膜中PKC信号传导部分相关。控制血糖水平的长期能力可能有助于减少每天注射胰岛素的频率。免疫组织化学显示，糖尿病视网膜中胶质纤维酸性蛋白表达的增加被该装置减弱。装置周围的皮下组织的组织学评估显示了装置的生物相容性。总之，胰岛素释放装置可减轻STZ诱导的糖尿病患者视网膜功能的降低达4周，并且该装置的功效可能与视网膜中PKC信号传导部分相关。控制血糖水平的长期能力可能有助于减少每天注射胰岛素的频率。胰岛素释放装置可减轻STZ诱导的糖尿病患者视网膜功能的降低达4周，并且该装置的功效可能与视网膜中PKC信号传导部分相关。控制血糖水平的长期能力可能有助于减少每天注射胰岛素的频率。胰岛素释放装置可减轻STZ诱导的糖尿病患者视网膜功能的降低达4周，并且该装置的功效可能与视网膜中PKC信号传导部分相关。控制血糖水平的长期能力可能有助于减少每天注射胰岛素的频率。