Diabetes: a gene therapy approach using genetically modified skin cells

Abstract

The long-term implications of deregulation of glucose metabolism, manifesting itself as diabetes is significant. Whilst treatments for the disease are progressing, often they require multiple daily insulin injections. This may be difficult for diabetics in poorer nations. This thesis examines the possibility of utilising keratinocytes and melanocytes transfected with either normal or furin-modified proinsulin constructs, to process and secrete mature insulin via secreted protein pathways. The advantage of this approach is that it may allow normalisation of basal glucose levels, which in turn may prevent or delay the onset of many of the complications associated with diabetes. The results confirmed that keratinocytes and melanocytes are able to process and secrete mature insulin from a furin-modified proinsulin construct, thus validating this approach and paving the way for skin grafts of genetically modified cells to be used as a possible treatment for diabetes. Whilst the results regarding the ability of these cells to process a normal proinsulin construct are inconclusive, they highlight areas of interest that could help to resolve this issue

Date of Award	2004
Original language	English