Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb

In this study, we demonstrate that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from hippocampus and olfactory bulb. Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampus and olfactory bulb-derived neural stem cells. Our analysis indicates that the balance between Wnt3, which triggers the expression of insulin via NeuroD1 transcription factor, and IGFBP-4, which inhibits the original Wnt3 action, is regulated depending on the diabetic status. We also show that adult neural progenitors derived from diabetic animals retain the ability to give rise to insulin-producing cells and that grafting neuronal progenitors into the pancreas of diabetic animals reduces glucose levels. This study provides an example of a simple and direct use of adult stem cells from one organ to another, without introducing additional inductive genes. In this study, we demonstrate that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from hippocampus and olfactory bulb. Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampus and olfactory bulb-derived neural stem cells. Our analysis indicates that the balance between Wnt3, which triggers the expression of insulin via NeuroD1 transcription factor, and IGFBP-4, which inhibits the original Wnt3 action, is regulated depending on the diabetic status. We also show that adult neural progenitors derived from diabetic animals retain the ability to give rise to insulin-producing cells and that grafting neuronal progenitors into the pancreas of diabetic animals reduces glucose levels. This study provides an example of a simple and direct use of adult stem cells from one organ to another, without introducing additional inductive genes.本研究证实，胰岛素不仅可在哺乳动物胰腺中产生，亦可在源自海马体（hippocampus）与嗅球（olfactory bulb）的成年神经元细胞中合成。旁分泌Wnt3（Paracrine Wnt3）在促进源自海马体及嗅球的神经干细胞中胰岛素的活跃表达过程中发挥不可或缺的核心作用。分析结果显示，通过NeuroD1转录因子（NeuroD1 transcription factor）触发胰岛素表达的Wnt3，与抑制Wnt3原有活性的IGFBP-4之间的动态平衡，会随机体糖尿病状态发生适应性调节。研究同时表明，源自糖尿病动物的成年神经前体细胞仍具备分化为胰岛素分泌细胞的能力，且将神经元前体细胞移植至糖尿病动物的胰腺内可有效降低血糖水平。本研究展示了一种无需引入额外诱导基因，即可直接将某一器官的成体干细胞跨器官应用的简洁可行范例。本研究证实，胰岛素不仅可在哺乳动物胰腺中产生，亦可在源自海马体（hippocampus）与嗅球（olfactory bulb）的成年神经元细胞中合成。旁分泌Wnt3（Paracrine Wnt3）在促进源自海马体及嗅球的神经干细胞中胰岛素的活跃表达过程中发挥不可或缺的核心作用。分析结果显示，通过NeuroD1转录因子（NeuroD1 transcription factor）触发胰岛素表达的Wnt3，与抑制Wnt3原有活性的IGFBP-4之间的动态平衡，会随机体糖尿病状态发生适应性调节。研究同时表明，源自糖尿病动物的成年神经前体细胞仍具备分化为胰岛素分泌细胞的能力，且将神经元前体细胞移植至糖尿病动物的胰腺内可有效降低血糖水平。本研究展示了一种无需引入额外诱导基因，即可直接将某一器官的成体干细胞跨器官应用的简洁可行范例。