Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes
Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes
复制标题
DOI：
10.1152/ajpendo.00180.2006
复制
发表时间：
2007-01-01
影响因子：
5.1
通讯作者：
Seino, Susumu
中科院分区：
文献类型：
--
作者：
Okuno, Masaaki;Minami, Kohtaro;Seino, Susumu
我们最近发现从正常成年小鼠分离的胰腺腺泡细胞在体外可以转分化为胰岛素分泌细胞。使用两种不同的1型糖尿病动物模型，我们在这里表明，胰岛素分泌细胞也可以从处于胰岛素绝对缺乏的糖尿病状态的啮齿动物的胰腺腺泡细胞中产生。当链脲佐菌素处理的小鼠胰腺腺泡细胞在低血清条件下，在表皮生长因子和烟酰胺的存在下，在悬浮培养，胰岛素基因的表达逐渐增加。此外，还诱导了其他胰腺激素的表达，包括胰高血糖素、生长抑素和胰多肽。通过基于Cre/loxP的直接细胞谱系追踪系统的分析显示，这些新制造的细胞来源于表达淀粉酶的胰腺腺泡细胞。高糖和其他促胰岛素分泌素可显著刺激新细胞分泌胰岛素。此外，从Komeda糖尿病易感大鼠（另一种1型糖尿病动物模型）的胰腺腺泡细胞产生胰岛素分泌细胞。本研究表明，胰岛素分泌细胞可以通过转分化产生的胰腺腺泡细胞的啮齿动物在糖尿病状态，并进一步表明，胰腺腺泡细胞代表了一个潜在的来源自体移植的胰岛素分泌细胞治疗1型糖尿病。
We recently found that pancreatic acinar cells isolated from normal adult mouse can transdifferentiate into insulin-secreting cells in vitro. Using two different animal models of type 1 diabetes, we show here that insulin- secreting cells can also be generated from pancreatic acinar cells of rodents in the diabetic state with absolute insulin deficiency. When pancreatic acinar cells of streptozotocin-treated mice were cultured in suspension in the presence of epidermal growth factor and nicotinamide under low-serum condition, expressions of insulin genes gradually increased. In addition, expressions of other pancreatic hormones, including glucagon, somatostatin, and pancreatic polypeptide, were also induced. Analysis by the Cre/loxP-based direct cell lineage tracing system revealed that these newly made cells originated from amylase-expressing pancreatic acinar cells. Insulin secretion from the newly made cells was significantly stimulated by high glucose and other secretagogues. In addition, insulin- secreting cells were generated from pancreatic acinar cells of Komeda diabetes-prone rats, another animal model of type 1 diabetes. The present study demonstrates that insulin- secreting cells can be generated by transdifferentiation from pancreatic acinar cells of rodents in the diabetic state and further suggests that pancreatic acinar cells represent a potential source of autologous transplantable insulin- secreting cells for treatment of type 1 diabetes.