Local Regulation of Endocrine Organ by Members of TGF family

在本研究中，我们研究了tgf - β表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tgf - β分别在胰岛的非β细胞和β细胞中表达。其次，激活素A和tgf - β都通过钙依赖的方式刺激胰岛素分泌。此外，这两种配体抑制atp敏感钾通道的活性，并通过电压依赖性钙通道增加钙的内流。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物。第三，激活素A表达于胰腺内皮细胞的内分泌前体细胞中，被认为在胰腺内分泌细胞的分化中发挥作用。与这一观点一致的是，激活素A将含有淀粉酶的胰腺AR42J细胞（一种具有类似胰腺前体细胞特征的细胞系）转化为神经元样细胞。此外，激活素a处理的AR42J细胞表达胰腺多肽，一种胰腺激素。因此，激活素A在胰腺中将AR42J细胞转化为内分泌细胞。

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.