Use of liposomes to introduce substances into pancreatic islet cells.

Abstract

The liposome technique is widely used to transport substances that cannot normally traverse the plasma membrane into the cell. The interactions of liposomes with the plasma membrane of pancreatic islet cells have not previously been studied. We evaluate the suitability of the liposome technique for introducing substances into the pancreatic beta-cell to which the cell membrane is impermeable. Liposomes were synthesized with an ether-injection method, and the cell-liposomal interactions were investigated by means of radioactive labeling and the fluorescent aqueous space marker 6-carboxyfluorescein. Experiments were performed on freshly isolated mouse pancreatic islets and on free islet cell preparations. With fluorescence microscopy, liposomes were observed to fuse spontaneously with islet cells, and the corresponding internalized volumes were quantified with spectrofluorometric measurements. The liposome association with islets and islet cell suspensions, as assessed by radioactive labeling, was found to increase with the liposome concentration. The effects of liposome membrane lipid composition on the fusion rate were found to be decreased in the presence of glucolipid. In addition, polyethylene glycol failed to affect the liposomal uptake. Freshly isolated islets incubated with liposomes containing glucose 6-phosphate were observed to release slightly more insulin than islets incubated with "empty" liposomes. In conclusion, liposomes fuse spontaneously with islet cells in vitro, and the uptake of liposomes is regulated by the lipid composition of the liposomal bilayer and the amount of liposomes present. The function of the beta-cell can be altered with the liposome technique, e.g., by addition of biologically active molecules such as glucose 6-phosphate.