Funding outcome

Diabetes mellitus is a common disease with a significant impact on children and the health care system. In severe Type I diabetics, there has been significant interest in using pancreatic islets that contain insulin and other important hormones to replace or reduce the amount of insulin administered to patients. Others have proposed using stem cells as a better source than islets. However, the gene network that regulates how stem cells become mature and functioning islet cells that secrete insulin and glucagon is not completely worked out. Recently, mutations in transcription factor genes have been identified in children and adolescents with Type II diabetes, including those from First Nations families. DLX genes are transcription factors that turn 'on' or 'off' target genes during embryonic development. 'Knockout' mice, with both DLXl and DLX2 mutated, die with multiple birth defects. We have determined that DLX genes are expressed in newborn and adult pancreatic islets in the same cells as those with insulin, glucagon and other hormones. We will use the Dlx1/Dlx2 double knockout mouse to determine the role of these genes in pancreas development. We have found that there is a significant reduction in the expression of insulin in the pancreas of the Dlx1/Dlx2 double knockout mouse. Subsequently, we have also discovered that DLX transcription factors bind directly to the insulin gene. We predict that loss of Dix gene function may contribute to Type II diabetes and DLX genes may be required for proper development and for maintenance of pancreatic islet cell function.