- Prof. Ann M. Simpson, Principal Investigator
- Dr. Ming Q. Wei, Co-Investigator
- Dr. Bronwyn O’Brien, Co-Investigator
- University of Technology Sydney, St. Leonards, Australia
- Correction of Diabetes Using Primary Liver Cells
Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. The chronic complication problems of diabetes and the lack of donor tissue for transplantation could theoretically be overcome by engineering from the patient's own cells an "artificial beta cell", i.e. a non-islet cell, capable of synthesising, storing and secreting mature insulin in response to metabolic stimuli, such as glucose. The ultimate goal of this technology is to deliver the insulin gene directly to a patient's own liver cells, which would regulate insulin secretion in response to glucose and other substances that stimulate insulin secretion, controlling blood glucose without the need for immunosuppression.
To accomplish this, the delivery of the insulin gene to primary liver cells (cells from and animal's or human's body) must be efficiently achieved. Results from our laboratory using a non-pathogenic viral delivery system indicate that we can reverse diabetes in chemically induced diabetic rats by expression of insulin and a beta cell transcription factor NeuroD. The aim of this study is to repeat this in an autoimmune model of diabetes, the non-obese diabetic mouse, which mimics very closely the onset of diabetes in humans. We will determine whether we can reverse diabetes in these animals and determine whether their response to glucose is normal over an extended period of time, with no attack by the factors of the immune system that stimulate the development of diabetes in humans.
The results from this research proposal should lead to the delivery of the insulin gene to large numbers of primary liver cells that store and secrete insulin in response to glucose stimuli. These cells would control blood glucose levels in patients without the need for immunosuppression.