Funded Research

The worldwide increase in the incidence of type 2 diabetes, which is now even being documented in young children, demands the development of new drugs for the safe and effective treatment of the disease. Such new drugs would also have beneficial effects in limiting the risk of costly long-term complications, which ultimately will have a burden on the NHS. The naturally occurring gut hormone, glucose-dependent insulinotropic polypeptide (GIP), has recently emerged as an important new drug candidate for the potential treatment of type 2 diabetes. Exciting research data published by Japanese scientists using transgenic mice suggests that circulating GIP directly links obesity and insulin resistance to diabetes. Therefore, by selectively blocking the biological actions of GIP (antagonism) it should be possible to alleviate insulin resistance and ultimately type 2 diabetes. Pilot studies in the applicant’s laboratory have shown the ability of a novel GIP antagonist to improve tissue insulin sensitivty and glucose tolerance in an animal model of type 2 diabetes. This proposal will further develop and test novel, longer-acting forms of GIP-receptor antagonists, enhanced by optimal bioengineering and strategies to prevent rapid removal from the body. It is hoped that this research proposal will bring forward a new class of drug offering a safe and exciting therapeutic approach to diabetes.

Successful transplantation of islets (the part of the pancreas which makes insulin) or whole pancreas has allowed a limited number of people with diabetes to stop injecting insulin. Virtually normal glucose levels can be restored, preventing risk and fear of low glucose levels. More than one pancreas from a post mortem donor is required for every individual who benefits and most people have to re-start insulin injections in the longer term. Current donor rates are only enough for 1% of people with insulin-dependent Type 1 diabetes. During normal pregnancy, islets become considerably larger and are able to produce much higher levels of insulin. Evidence from animal studies suggests that this may be driven by increases in a range of hormones (prolactin, placental lactogen, growth hormone and insulin like growth factor 1). We will test the potential of these hormones to enhance overall health, size and insulin secretion of human islets before transplantation. We believe that previously untested combinations of these factors with another hormone found in normal people which increases insulin release (GLP1) are particularly likely to produce exciting results. The lessons learned from these focussed short-term studies will have an immediate impact on the way islets are prepared for clinical transplantation within the UK programme. Indeed it is hoped that pre-treatment of the cells with these hormones will enable reproducible sustained liberation from insulin injections following a single transplant procedure using islets from only one donor. The present work will lead on naturally to more detailed studies to understand the effects of these hormones on the insulin-producing cells. It is hoped that this in turn will lead to new tablet treatments to prevent progression of diabetes towards a need for insulin injections.