Diabetes

Diabetes is a disease characterised by a failure to regulate blood glucose levels correctly. Untreated or uncontrolled diabetics have high levels of blood glucose and this can result in a variety of serious long-term complications. Normally, glucose transport from blood to tissues depends on the hormone insulin, secreted from the beta cells of the pancreas. There are two types of diabetes. In type 1 diabetes, the beta cells of the pancreas are lost, and sufferers have to be treated with regular doses of insulin. In type 2 diabetes some of the tissues in the body (e.g. fat and muscle) can’t respond to insulin. However, this is a complex and varied disease and patients also have some pancreatic pathology. Because of this, many type 2 diabetics also require insulin treatment. Despite the availability of insulin treatment, patients may suffer from a variety of long-term complications which may be highly debilitating, including heart disease, kidney disease, stroke and blindness. The reason for this is that even the most sophisticated regime of insulin dosage cannot replicate the fine control of insulin secretion which is exerted by the blood glucose on normal beta cells. This consideration has meant that much research has gone into methods for transplanting beta cells into diabetic patients, thereby producing a cure. But islet cell transplants involve serious problems of donor supply and immune rejection. One way forward is to create new beta cells by transdifferentiation of liver to pancreas. Our work suggests the possibility of creating beta cells from the liver cells of the patient, which could then be used for transplantation. An alternative possibility would be to administer the appropriate gene to the patient and directly convert some of the liver cells to beta cells in situ.

Either of these strategies could help overcome the problems of insulin therapy and of islet cell transplantation and help to reduce the long-term complications.

150 million people worldwide currently suffer from diabetes and that number is predicted to rise to 300 million over the next 20 years. This rapid increase is largely due to increased prosperity leading to dietary changes which predispose to type 2 diabetes. Although only a minority of these cases will require insulin treatment, the market is very large and will certainly increase rapidly.