Funded Research

SPARC (Secreted Protein, Acidic and Rich in Cysteine) is a protein produced in all tissues, but especially in body fat (adipose tissue). SPARC promotes scarring of fat tissue. Whilst fat tissue is progressively scarred in obesity, our latest findings show that SPARC levels are elevated in subjects with obesity as well as insulin resistance suggesting a key role of SPARC in linking obesity to the development of diabetes. Scarring restricts deposition of surplus dietary fats which are in the circulation in the form of lipid into fat tissue. These surplus lipids are subsequently diverted to pathological lipid deposits in inner organs leading to obesity related complications, insulin resistance and eventually to Type 2 diabetes. This project examines the existence of genetic SPARC variants with the aim to identify a form of SPARC which is at the same time genetically expressed in fat and blood cells and which may not only mirror SPARC’s regulation in fat tissue but relate to obesity related complications and diabetes. This will subsequently allow analyses of data from epidemiological cohorts derived from blood samples rather than fat tissue. The investigators hope to identify SPARC variants which are suitable new risk markers and which may lend itself as a new therapeutic target.

Type 2 Diabetes develops when the pancreas fail to release enough insulin to meet demand due to both decreased function of pancreatic beta-cells and through loss of beta-cell number. The current study aims to investigate how an enzyme important in regulating the function of insulin secretion (glucokinase) binds to a protein important in regulating beta-cell number (BAD) and will determine whether communication between these two proteins provides a link between the regulation of beta-cell function and beta-cell mass. Understanding these mechanisms is essential to enable the development of new treatments for Type 2 Diabetes.

People with diabetes may not know exactly when their foot makes contact with the ground while walking because of the lack of sensation in their feet. This will mean that their muscles, which are already weakened, may not react quickly enough to adequately support the body. The major muscles of the leg in people with diabetes are weaker than those of individuals without diabetes, which may mean that people with diabetes are operating closer to their muscle’s maximum capacity when walking and performing everyday tasks. These factors are likely to increasing the chance of people with diabetes falling and injuring themselves. This project will identify problems that people with diabetes face when walking and performing other everyday tasks such as going up and down stairs. People will be assessed during these everyday activities in our laboratory by measuring the body’s movement and muscle responses as they walk. A special device monitoring eye movements will test whether people with diabetes look closer to their feet as they walk to compensate for the lack of sensation in their feet. This work will help us to understand the reasons why walking may become dangerous for people with diabetes and may lead to the development of strategies or interventions that help make everyday tasks safer for people with diabetes.

Fat tissue in obese people is affected by a form of inflammation, and this is thought be important in the development of diabetes. A family of proteins known as metalloproteinases may contribute to causing diabetes, by controlling this inflammation and affecting how fat tissue changes in size when we gain weight. We want to expose fat cells from healthy non-diabetic people to conditions in the laboratory that mimic inflammation and diabetes, to see how the levels of these metalloproteinases change in response to this. Doing so will allow us to start understanding the function of these proteins, and help us to develop new diagnostic tests and new drugs for treating and preventing diabetes in the future.