Cellular interaction between mouse pancreatic α-cell and β-cell lines:: Possible contact-dependent inhibition of insulin secretion

Cellular interaction between mouse pancreatic α-cell and β-cell lines:: Possible contact-dependent inhibition of insulin secretion
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DOI:
10.1177/153537020322801020
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发表时间:
2003-11-01
影响因子:
3.2
通讯作者:
Sakata, T
Sakata, T
中科院分区:
医学4区
文献类型:
--
作者:
Hamaguchi, K;Utsunomiya, N;Sakata, T

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胰岛中的内分泌细胞在异型细胞和同型细胞之间具有细胞通讯。进行本研究以利用分化的小鼠细胞系(即,α TC克隆6和β TC细胞)。这两种细胞系在旋转摇床上共培养48 h内产生大量大小均匀的细胞聚集体。胰岛素和胰高血糖素的免疫组织化学染色表明,β TC细胞位于每个聚集体的中心核心,而α TC细胞形成围绕β TC细胞的套层。无论所用的两种细胞类型的比例如何,都观察到这种分离。尽管10(-8)M或更高浓度的胰高血糖素刺激单层和聚集体中β TC细胞的胰岛素分泌,但聚集体培养物中α TC/β TC细胞比率的增加伴随着分泌的胰岛素减少和β TC组分的细胞内胰岛素含量的增加。alphaTC细胞对betaTC胰岛素分泌的抑制作用并不局限于聚集体培养,因为通过alphaTC与betaTC细胞单层共培养,betaTC细胞的胰岛素分泌也受到抑制,细胞内胰岛素含量增加。另一方面,β TC细胞分泌的和细胞内的胰岛素不受TranswelTM共培养系统中的α TC细胞的影响,在该共培养系统中,通过允许通过培养基代谢物进行化学通讯的半透膜防止了细胞与细胞的直接接触。这些数据表明,β TC细胞的胰岛素分泌可能由于与α TC细胞接触而受到抑制。
The endocrine cells in the pancreatic islet have cellular communication between the heterotypic cells as well as the homotypic cells. The present study was conducted to elucidate the cellular interaction between pancreatic alpha cells and beta cells utilizing differentiated mouse cell lines (i.e., alphaTC clone 6 and betaTC cells). Co-culture of these two cell lines on a gyratory shaker generated numerous cellular aggregates of homogenous size within 48 h. lmmunohistochemical staining for insulin and glucagon demonstrated that betaTC cells were located in the central core of each aggregate, while alphaTC cells formed a mantle layer surrounding the betaTC cells. This segregation was observed regardless of the ratios of the two cell types employed. Although glucagon at concentrations of 10(-8) M or higher stimulated insulin secretion from betaTC cells in both monolayer and aggregates, an increase in the ratio of alphaTC/betaTC cells in aggregate cultures was accompanied by a decrease in secreted insulin and a rise in intracellular insulin content of the betaTC component. The inhibitory effect of alphaTC cells on betaTC insulin secretion was not limited to aggregate culture, since insulin secretion from betaTC cells was also suppressed, and intracellular insulin content increased, by co-culture of alphaTC with betaTC cells in monolayer. On the other hand, the secreted and intracellular insulin of betaTC cells was not affected by alphaTC cells in a TranswelI(TM) co-culture system in which direct cell-to-cell contacts were prevented by a semipermeable membrane that permitted chemical communication via medium metabolites. These data suggest that the insulin secretion from betaTC cells may be inhibited possibly as a result of the contact with alphaTC cells.