Cellular Interaction Between Mouse Pancreatic α-Cell and β-Cell Lines: Possible Contact-Dependent Inhibition of Insulin Secretion

Abstract

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 α cells and β cells utilizing differentiated mouse cell lines (i.e., αTC clone 6 and βTC cells). Co-culture of these two cell lines on a gyratory shaker generated numerous cellular aggregates of homogenous size within 48 h. Immunohistochemical staining for insulin and glucagon demonstrated that βTC cells were located in the central core of each aggregate, while αTC cells formed a mantle layer surrounding the βTC 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 βTC cells in both monolayer and aggregates, an increase in the ratio of αTC/βTC cells in aggregate cultures was accompanied by a decrease in secreted insulin and a rise in intracellular insulin content of the βTC component. The inhibitory effect of αTC cells on βTC insulin secretion was not limited to aggregate culture, since insulin secretion from βTC cells was also suppressed, and intracellular insulin content increased, by co-culture of αTC with βTC cells in monolayer. On the other hand, the secreted and intracellular insulin of βTC cells was not affected by αTC cells in a Transwell™ 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 βTC cells may be inhibited possibly as a result of the contact with αTC cells.