NICOTINAMIDE IS A POTENT INDUCER OF ENDOCRINE DIFFERENTIATION IN CULTURED HUMAN FETAL PANCREATIC-CELLS
NICOTINAMIDE IS A POTENT INDUCER OF ENDOCRINE DIFFERENTIATION IN CULTURED HUMAN FETAL PANCREATIC-CELLS
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DOI：
10.1172/jci116723
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发表时间：
1993-09-01
影响因子：
15.9
通讯作者：
HAYEK, A
中科院分区：
文献类型：
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作者：
OTONKOSKI, T;BEATTIE, GM;HAYEK, A
采用组织培养法研究了烟酰胺（NIC）对人胚胎和成人胰腺内分泌细胞的影响。用10 mM NIC处理胎儿细胞导致DNA含量增加两倍，胰岛素含量增加三倍。这与未分化上皮细胞簇的β细胞生长的发展以及胰岛素、胰高血糖素和生长抑素基因表达的增加有关。DNA合成仅在未分化的细胞中受到刺激。NIC促胰岛素和促有丝分裂作用的半数最大剂量分别为5-10和1-2 mM。与NIC培养的胰岛样细胞簇对葡萄糖刺激有反应，胰岛素释放呈双相增加（四倍峰值），而对照细胞对葡萄糖无反应。移植到裸鼠体内后，对照组和NIC处理组细胞均发育为功能性胰岛组织。与成人胰岛相比，NIC的促胰岛素作用只能在胎儿细胞中表现出来。我们的研究结果表明，NIC诱导人胎胰岛细胞的分化和成熟。该模型对于研究β细胞发育的分子机制是有用的。
The effects of nicotinamide (NIC) on human fetal and adult endocrine pancreatic cells were studied in tissue culture. Treatment of the fetal cells with 10 mM NIC resulted in a twofold increase in DNA content and a threefold increase in insulin content. This was associated with the development of beta cell outgrowths from undifferentiated epithelial cell clusters and an increase in the expression of the insulin, glucagon, and somatostatin genes. DNA synthesis was stimulated only in the undifferentiated cells. Half-maximal doses for the insulinotropic and mitogenic effects of NIC were 5-10 and 1-2 mM, respectively. Islet-like cell clusters cultured with NIC responded to glucose stimulation with a biphasic increase in insulin release (fourfold peak), whereas control cells were unresponsive to glucose. Both control and NIC-treated cells developed into functional islet tissue after transplantation into athymic nude mice. As compared with adult islets, the insulinotropic action of NIC could only be demonstrated in the fetal cells. Our results indicate that NIC induces differentiation and maturation of human fetal pancreatic islet cells. This model should be useful for the study of molecular mechanisms involved in beta cell development.