Regeneration Therapy Diabetes Using the Pancreatic Stem Cell System

使用胰腺干细胞系统再生治疗糖尿病

• 批准号: 13470222
• 负责人: KOJIMA Itaru
• 金额: $ 9.34万
• 依托单位: Institute for Molecular and Cellular Regulation, Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470222/
• 关键词: regeneration medicine; insulin; pancreatic stem cell; differentiation; diabetes mellitus; activin; betacellulin; 膵β細胞; 幹細胞

The final goal of our study is to establish a new therapeutic approach for treatment of type II diabetes. In the present study, we investigate to elucidate the characteristics of the pancreatic stem cells and regulatory mechanism for the regulation of growth and differentiation of these cells. We first studied the changes in the expression of transcription factors during the differentiation of AR42J, a model of the pancreatic stem cells, during differentiation to insulin-producing cells. We found that activin A induced differentiation to endocrine cells and neurogeninB is a critical transcription factor. We then studied the changes in the expression of activin A in the pancreatic duct after reduction of the beta cell mas. We found that the expression of activin A was induced after the reduction of the beta cell mass. Given that activin A is a critical differentiation factor for the pancreatic stem cells, the induction of acivin A in the pancreatic duct may be a crucial step for the initiation of the beta cell neogenesis. Finally, we extablished a culture of the pancreatic ductal cells and found that these cells differentiate into insulin-secreting cells after the treatment with a combanation of activn A and betacellulin. We are currently studying the properties of differentiated cells.

我们研究的最终目标是建立一种新的治疗II型糖尿病的治疗方法。本研究旨在阐明胰腺干细胞的特性及其生长和分化的调控机制。我们首先研究了在胰腺干细胞的模型AR42J分化为胰岛素产生细胞的过程中转录因子表达的变化。我们发现激活素A诱导内分泌细胞分化，神经生成素B是一个关键的转录因子。然后，我们研究了β细胞质量减少后胰管中激活素A表达的变化。我们发现激活素A的表达在β细胞群减少后被诱导。鉴于激活素A是胰腺干细胞的关键分化因子，胰腺导管中激活素A的诱导可能是启动β细胞新生的关键步骤。最后，我们建立了胰腺导管细胞的培养，发现这些细胞在用activn A和β细胞素组合处理后分化为胰岛素分泌细胞。我们目前正在研究分化细胞的特性。

项目成果

Endocrinology. 142. 5379-5385 (2001)

内分泌学。

Huang, W.H., Shen, L, Eto, Y., Kojima. I and Gaisano, H.: "Effects of selective exocrine o rendocrine induction of AR42J on SNARE and Munc18 expression"Pancreas. 25. 56-63 (2002)

黄W.H.、沉L、江藤Y.、小岛。

Fujimaki, S., Kubohara, Y., Kobayashi, I., Kojima, I.: "Caspase-independent apoptosis induced by DIF in INS-I cells"Eur.J.Pharmacol.. 421. 93-100 (2001)

Fujimaki, S.、Kubohara, Y.、Kobayashi, I.、Kojima, I.：“INS-I 细胞中 DIF 诱导的不依赖半胱天冬酶的细胞凋亡”Eur.J.Pharmacol.. 421. 93-100 (2001)

Kojima, H., Nakamura, T. et al.: "Combined expression of PDX-1 and lsl-1 induces immature enterocytes to produce insulin"Diabetes. 51. 1398-1409 (2002)

Kojima, H.、Nakamura, T. 等人：“PDX-1 和 lsl-1 的组合表达诱导未成熟的肠上皮细胞产生胰岛素”糖尿病。

Zhang, Y.Q., Zhang, H., Maeshima, A., Miyagawa, I., Kojima, I.: "Up-regulation of the expression of activins in the pancreatic duct by reduction of the β cell mass"Endocrinology. 143. 3540-3547 (2002)

张，Y.Q.，张，H.，前岛，A.，宫川，​​I.，小岛，I.：“通过减少β细胞量上调胰管中激活素的表达”内分泌学143。 3540 -3547 (2002)