Gene and cell-replacement therapy in the treatment of type 1 diabetes - How high must the standards be set?

Recent advances in molecular and cell biology may allow for the development of novel strategies for the treatment and cure of type 1 diabetes. In part icular, it is now possible to envisage restoration of insulin secretion by gene or cell-replacement therapy. The beta -cell is, however, remarkably so phisticated, and many of the features of this highly differentiated secreto ry cell will have to be faithfully mimicked in surrogate cells. In particul ar, insulin is normally secreted in a well-regulated fashion in rapid respo nse to the metabolic needs of the individual and most specifically (but not exclusively) to changes in circulating levels of glucose. Such regulated s ecretion will be indispensable in order to avoid both hyper- and hypoglycem ic episodes and depends on the ability of cells to store insulin in secreto ry granules before exocytosis in response to physiological stimuli. Further more, any newly created insulin-secreting cell will have to be able to adap t to alterations in insulin requirements that accompany changes with exerci se, body weight, and aging. Fine tuning of insulin secretion over the longe r term will also be important to avoid "clinical shifting" that could be ca used by over-insulinization, including increased adiposity and cardiovascul ar disease. Finally, it will be necessary to ensure that newly created or i mplanted (surrogate) beta -cells are protected in some way from recognition by the immune system and in particular from autoimmune destruction.