Funded Research

Diabetes arises from the inability of the beta cells of the islets of Langerhans to secrete adequate amount of insulin to keep blood glucose low. Researchers have focused their attention to understanding the physiology of beta cells in order to identify new pharmacological tools or opportunities for intervention to treat diabetes. Unfortunately only a limited amount of biological islet material of human origin is available for research, thus alternative models to study human physiology are needed and they are represented mainly by islets isolated from other mammals such as mice and pigs. We will compare islets of these three species (human, pig, mouse) to identify what differences exist in terms of the mechanisms that allow increases in glucose to stimulate insulin secretion. We aim to understand what are the best conditions to work with these models in order to be able to fully translate the data obtained with Islets from mice and pigs onto human physiology.

The alarming increase in type 2 diabetes is primarily owing to the growing prevalence of obesity and aging. Metabolic syndrome (MetS) is a clustering of cardiovascular disease risk factors, including obesity, diabetes and high blood pressure, that affects 1 in 4 adults in the UK. It is associated with increased risk of heart disease, cancer and dementia (including Alzheimer’s disease) and death. Therefore there is a growing need for new targets in order to develop novel therapies and provide earlier diagnosis in order to provide the most effective treatment. Excessive Abeta peptide production underlies the development of Alzheimer’s disease and our recent work in mice has demonstrated a clear connection between increased Abeta production, notably the species Abeta42, and metabolic dysfunction. The major question now is whether this process is also happening in humans? Therefore we aim to determine whether serum Abeta levels can be a bio-marker for the severity of metabolic syndrome and the associated cardiovascular complications.

Diabetic ulcers (DFUs) are a far too common complication of diabetes. Many times these wounds are unable to heal because there are changes in how cells respond to the instructions to repair damaged tissue. This research aims to understand how small molecules called microRNAs (essentially one form of a cells version of computer code), work together to alter how cells respond to external signals from their environment, and their potential use as a therapeutic. These microRNAs are unique because they work similar to a conductor in an orchestra, finely tuning and co-ordinating many players in the machinery that interprets how cells respond to stimuli. The hypothesis of this work is that these microRNAs, when combined with each other, provide therapeutic benefits that exceed their individual contributions. Due to the fact that many times cells within DFUs display changes to the way they respond to instructions to repair damaged tissue, microRNAs present a potentially powerful strategy for altering their behaviour and promoting timely wound repair.

The current global epidemic of obesity and type 2 diabetes (T2D) has been partly fuelled by the propagation of these diseases from parent to child across one or more generations. T2D develops when the function of insulin-secreting cells in the pancreas is impaired. Very few studies, however, have investigated underlying mechanisms within these cells that may explain transmission of T2D from mother to child. In recent years, there has been increasing interest in the role of epigenetics, which is the study of biological mechanisms that establish and maintain whether genes are switched on or off, in the development of T2D. This is largely due to the fact that unlike the genome of an individual, which is largely stable, the epigenome can be reversibly modified by exposure to nutritional and environmental factors e.g. obesity. The aim of this project is, therefore, to determine the impact of maternal obesity on the transmission of T2D risk to the offspring and to characterise epigenetic changes that may provide a mechanism for this event.