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OBESITY AND DIABETES: PATHOPHYSIOLOGICAL MECHANISMS AND THERAPEUTIC APPROACHES

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

Department of Anatomy, Biology and Medicine, Oita Medical University School of Medicine, Oita, Japan

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 cells and ß cells utilizing differentiated mouse cell lines (i.e., TC clone 6 and ßTC 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 ßTC cells were located in the central core of each aggregate, while TC cells formed a mantle layer surrounding the ßTC 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 ßTC cells in both monolayer and aggregates, an increase in the ratio of TC/ßTC cells in aggregate cultures was accompanied by a decrease in secreted insulin and a rise in intracellular insulin content of the ßTC component. The inhibitory effect of TC cells on ßTC insulin secretion was not limited to aggregate culture, since insulin secretion from ßTC cells was also suppressed, and intracellular insulin content increased, by co-culture of TC with ßTC cells in monolayer. On the other hand, the secreted and intracellular insulin of ßTC cells was not affected by TC cells in a Transwell^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 ßTC cells may be inhibited possibly as a result of the contact with TC cells.

Key Words: cell-to-cell interaction • aggregate • pseudoislet • gyratory culture • pancreatic -cell and ß-cell lines

This article has been cited by other articles:

				J. Jo, M. Y. Choi, and D.-S. Koh Size Distribution of Mouse Langerhans Islets Biophys. J., October 15, 2007; 93(8): 2655 - 2666. [Abstract] [Full Text] [PDF]