Local Regulation of Endocrine Organ by Members of TGF family

TGF家族成员对内分泌器官的局部调节

• 批准号: 05454315
• 负责人: KOJIMA Itaru
• 金额: $ 4.16万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454315/
• 关键词: TGF-beta; activin A; pancreatic endocrine cell; differentiation; insulin; calcium; autocrine; paracrine; パラクリン機構; オートクリン機構; 局所因子; 分化誘導因子; 増殖因子

In the present research, we studied the role of members of TGF-beta supergene family in the regulation of pancreatic endocrine cell. We obtained the following results. First, we showed that activin A and TGF-beta are expressed in non-beta and beta-cells of the pancreatic islet, reapectively. Second, both activin A and TGF-beta stimulate insulin secretion by calcium-dependent manners. Furthermore, these two ligands inhibit the activity of the ATP-sensitive potassium channel and increase calcium influx via voltage-dependent calcium channel. This mode of action resembles that of glucose, a major stimulant of insulin secretion. Third, activin A is expressed in endocrine precursor cells found in pancreatic anlage and is thought to play a role in the differentiation of pancreatic endocrine cells. Consistent with this notion, activin A converted amylase-containing pancreatic AR42J cells, a cell line possessing characteristics similar to pancreatic precursor cells, into neuron-like cells. Furthermore, activin A-treated AR42J cells express pancreatic polypeptide, a pancreatic hormone. Hence, activin A converts AR42J cells into endocrine cells in pancreas.

本研究旨在探讨转化生长因子-β超基因家族成员在胰腺内分泌细胞调控中的作用。我们得到了以下结果。首先，我们发现激活素A和转化生长因子-β分别在胰岛的非β细胞和β细胞中表达。第二，激活素A和转化生长因子β均通过钙依赖的方式刺激胰岛素的分泌。此外，这两种配体抑制ATP敏感性钾通道的活性，并通过电压依赖性钙通道增加钙内流。这种作用模式类似于葡萄糖的作用模式，葡萄糖是胰岛素分泌的主要刺激剂。第三，激活素A表达于胰岛的内分泌前体细胞，并被认为在胰腺内分泌细胞的分化中起作用。与这一概念一致，激活素A将含有淀粉酶的胰腺AR42J细胞转化为神经元样细胞，该细胞具有与胰腺前体细胞相似的特征。此外，激活素A处理的AR42J细胞表达胰多肽，这是一种胰腺激素。因此，激活素A可以将胰腺中的AR42J细胞转化为内分泌细胞。

项目成果

Ohnishi, H et al.: "Conversion of amylase-containing rat pancreatic Ar42J cells to neuronlike cells by activin A" J.Clin.Invest.95. 2304-2314 (1995)

Ohnishi, H 等人：“通过激活素 A 将含有淀粉酶的大鼠胰腺 Ar42J 细胞转化为神经元样细胞”J.Clin.Invest.95。

Furukawa, M.et al.: "Initiation of insulin secretion from rat pancreatic islet in the absence glucose by activin A." Mol.Cell.Endocrinol.113. 83-87 (1995)

Furukawa, M.et al.：“在缺乏葡萄糖的情况下，激活素 A 启动大鼠胰岛分泌胰岛素。”

Ohnishi H.,et al.: "Conversion of amylase-containing pancreatic AR42J cells to neuron-like cells by activin A" Journal of Clinical Investigation. 95. 2304-2314 (1995)

Ohnishi H.,et al.：“通过激活素 A 将含有淀粉酶的胰腺 AR42J 细胞转化为神经元样细胞”临床研究杂志。

Furukawa M.,et al.: "Initiation of insulin secretion from rat pancreatic islet in the absence of glucese by activin A." Mollecular and Cellular Endocrinology. 113. 83-87 (1995)

Furukawa M.,et al.：“在缺乏葡萄糖的情况下，激活素 A 启动大鼠胰岛分泌胰岛素。”

Kojima,I.,Mogami,H.,Kawamura,N.and Shibata,H.: "Activin A inhibits cell-cycle progression induced by insulin-like growth factor-I" J.Endocrinol.137. 99-105 (1993)

Kojima,I.、Mogami,H.、Kawamura,N. 和 Shibata,H.：“激活素 A 抑制胰岛素样生长因子-I 诱导的细胞周期进展”J.Endocrinol.137。