Diabetes - Needs

Although insulin and today's medicines make a huge difference to patients' lives, blood glucose levels can still fall too far, causing 'sugar lows' (hypoglycaemia).

Symptoms including feeling shaky, sweating, tingling in the lips, going pale, heart pounding, confusion and irritability can result. If hypoglycaemia is not treated with a quick sugar 'fix' and a more substantial snack, it can lead to loss of consciousness. Therefore, ongoing research is looking both to understand how insulin operates normally and in disease and for better treatments for diabetess.

An ideal treatment for diabetes might be to provide new pancreas islets, (these are where the beta cells that make insulin are found). Some patients have already received cell transplants from donors. But there are two problems: not enough donors and patients need to receive immunosuppressive drugs for the rest of their lives.

Genetically engineering the patient's beta cells and putting them back in the pancreas might offer an alternative. A different approach is to convert liver cells into pancreas cells. Another possibility is to use stem cells. These are the relatively non-specialist cells found, for example in bone marrow, that become specialised. There has been some success in making beta-like cells that produce insulin in response to glucose. We are a long way from using engineered cells in treatment. One vital aspect will be to understand how the pancreas, the insulin factory, develops.

Finding out which genes are essential to development requires work with living creatures. These do not always have to be mammals - great insights have been achieved with humble nematode worms, flies and fish. But a vital organ such as the pancreas does require mice to be used in order to see which genes are switched on at different stages and what the proteins they code for are doing.

It has been know for some 20 years now that the protein Ptf1a is involved in the development of the pancreas. By comparing normal mice and mice bred without this protein it has been found Ptf1a helps cells to decide what they will become. It is turned on very early in all the cells that will eventually form the pancreas and then switches off in those pancreas cells that will eventually go on to make hormones like insulin.

Perhaps Ptf1a could be used to turn stem cells into pancreas cells, which would form part of the cell transplant process for diabetics.

Other research is concentrating on new targets for medicines. For example, what hinders the beta cells in the pancreas from releasing insulin? One culprit is an enzyme called DPP-IV which breaks down proteins that stimulate the release of insulin. Therefore, a medicine that inhibited DPP-IV might be able to treat diabetes in a new way. Finding chemicals that stop DPP-IV from working in the test tube is reasonably easy. But that does not mean in a patient they will be any good.

Medicines have to be swallowed or injected, they have to travel to their target, they have to avoid being turned into something toxic or into something that loses its effectiveness. Before asking a patient to stop taking his or her existing medication, researchers will want some confidence that the new one is likely to do the job. And, for the present, that means giving it to a creature that has many features in common with us. From their genes to their vital organs mammals are very similar.

Indeed in 1999, a likely chemical was found that inhibits pure human DPP-IV in the laboratory. It has been shown since then to inhibit DPP-IV in rats that mimic Type 2 diabetes, improving insulin secretion and glucose tolerance. So there is confidence that the chemical will do what it is meant to do if it reaches its target. The next stage was to give the chemical to dogs, as their metabolism in this regard is closer to humans. This was to confirm that DPP-IV was no longer breaking down the proteins needed to make insulin. The new chemical has now been give to a small number of type 2 diabetics for a 4-week period. The next stage is large-scale clinical trials.

Next Section: Role of Animals