Electrofusion-derived BRIN-BD11 cells are glucosesensitive insulin-secreting cells which provide an archetypal bioengineered surrogate β-cell for insulin replacement therapy in diabetes mellitus, 5x106BRIN-BD11 cells were implanted intraperitoneally into severely hyperglycaemic (>24mmol/l) streptozotocin-induced insulin-treated diabetic athymic nude (nu/nu) mice. The implants reduced hyperglycaemia such that insulin injections were discontinued by 5–16 days (<17mmol/l) and normoglycaemia (<9mmol/l) was achieved by 7–20 days. Implanted cells were removed after 28 days and re-established in culture. After re-culture for 20 days, glucose-stimulated (16.7mmol/l) insulin release was enhanced by 121% (p<0.001) compared to non-implanted cells. Insulin responses to glucagon-like peptide-1 (10−9mol/l), cholecystokinin-8 (10−8mol/l) and L-alanine (10 mmol/l) were increased by 32%, 31% and 68% respectively (p<0.05–0.01). Insulin content of the cells was 148% greater at 20 days after re-culture than before implantation (p<0.001), but basal insulin release (at 5.6 mmol/l glucose) was not changed. After re-culture for 40 days, insulin content declined to 68% of the content before implantation (p<0.01), although basal insulin release was unchanged. However, the insulin secretory responses to glucose, glucagonlike peptide-1, cholecystokinin-8 and L-alanine were decreased after 40 days of re-culture to 65%, 72%, 73% and 42% respectively of the values before implantation (p<0.05–0.01). The functional enhancement of electrofusion-derived surrogate β-cells that were re-cultured for 20 days after implantation and restoration of normoglycaemia indicates that thein vivoenvironment could greatly assist β-cell engineering approaches to therapy for diabetes.
将 5x106BRIN-BD11 细胞腹腔植入严重高血糖（24mmol/l）的链脲佐菌素诱导的胰岛素治疗糖尿病裸鼠（nu/nu）。植入细胞降低了高血糖，使小鼠在 5-16 天（<17mmol/l）内停止注射胰岛素，并在 7-20 天内达到正常血糖（<9mmol/l）。植入的细胞在 28 天后被移除，并重新进行培养。重新培养 20 天后，葡萄糖刺激的（16.7 毫摩尔/升）胰岛素释放量比未植入细胞增加了 121%（p<0.001）。胰岛素对胰高血糖素样肽-1（10-9mol/l）、胆囊收缩素-8（10-8mol/l）和L-丙氨酸（10 mmol/l）的反应分别增加了32%、31%和68%（p<0.05-0.01）。重新培养 20 天后，细胞中的胰岛素含量比植入前增加了 148%（p<0.001），但基础胰岛素释放量（5.6 毫摩尔/升葡萄糖）没有变化。再培养 40 天后，胰岛素含量下降到植入前的 68%（p<0.01），但基础胰岛素释放量没有变化。然而，对葡萄糖、胰高血糖素样肽-1、胆囊收缩素-8 和 L-丙氨酸的胰岛素分泌反应在再培养 40 天后分别降至植入前的 65%、72%、73% 和 42%（p<0.05-0.01）。植入后再培养 20 天的电融合衍生代用 β 细胞功能增强，血糖恢复正常，这表明体内环境可以极大地帮助 β 细胞工程方法治疗糖尿病。
