Recent advances in insulin gene therapy for type 1 diabetes

Type 1 diabetes results from the loss of insulin-producing pancreatic β cells following the action of β-cell-specific autoimmune responses. One possible treatment for type 1 diabetes is the development of β-cell substitutes by introducing an insulin-producing gene into non-β cells, which would evade the β-cell-specific autoimmune attack. However, this approach has been hampered by the absence of (1) an appropriate glucose-sensing system to regulate insulin gene transcription; (2) enzymes that process proinsulin to insulin; and (3) glucose-regulatable exocytosis in the target cells. Recent attempts to solve these problems have sought new methods for effective gene transfer and have addressed issues such as the expression and release of insulin in response to the physiological stimulus of glucose, the production of biologically active insulin, and the selection of an ideal target cell for the expression of the insulin gene.