- 2010Pump Priming
Analysis of tethering factors in the regulation of Glut4 spatial dynamicsRecipient:Professor Gwyn GouldInstitution:University of GlasgowCity:GlasgowAmount:£20,000.00Description: Insulin stimulates glucose transport into fat and muscle by promoting the movement of specialised transporter proteins from an internal storage depot to the cell surface. These transporter proteins function as specialised doorways through which glucose can move from the blood into fat and muscle for storage after a meal. By increasing the number of 'doorways' present in the boundary membrane of cells, insulin drives glucose into storage organs. This key action of insulin is known to be impaired in type 2 diabetes, resulting in insulin resistance and aberrant glucose homeostasis. This proposal is directed towards understanding how the distribution of these doorways is controlled within fat cells.
- 2010Pump Priming
Are human SPARC isoforms suitable peripheral makers of insulin resistance and diabetes-related complications?Recipient:Dr Katarina KosInstitution:Peninsula Medical School RecipientCity:PlymouthAmount:£19,260.00Description: 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.
- 2010The Professor David Matthews Non-Clinical Fellowship
Enteroviral infection as a causative factor in human type 1 diabetesRecipient:Dr Sarah RichardsonInstitution:Peninsula Medical School, PlymouthCity:PlymouthAmount:£164,547.00 (three years)Description: Our recent work has given substantial support to the hypothesis that enteroviruses might be a trigger for type 1 diabetes. It is now important to verify this by identifying which particular enteroviral serotype(s) are involved. In addition, we aim to develop a greater understanding of how these viruses can trigger the demise of the insulin-secreting beta cells. The research will make use of a unique collection of human pancreases obtained from patients who died soon after developing type 1 diabetes. We hope that this research will reveal whether viruses can trigger type 1 diabetes and that it will demonstrate how they do this.
- 2010Pump Priming
Investigation of the association between glucokinase and the pro-apoptotic protein BAD in pancreatic beta-cellsRecipient:Dr Catherine ArdenInstitution:Newcastle UniversityCity:NewcastleAmount:£13,665.00Description: 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.
- 2010Pump Priming
Investigation of the incretin pathway in Maturity onset diabetes of the young (MODY) secondary to heterozygous hepatocyte nuclear factor 1 alpha (HNF1A) gene mutationsRecipient:Dr Gaya ThanabalasinghamInstitution:Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM)City:OxfordAmount:£19,211.40Description: After eating a meal hormones are produced by the gut (called incretin hormones) which promote insulin release from the pancreas and lead to lowering of blood sugar levels. In diabetes there are defects in the production and action of these incretin hormones. Recently medications that target incretin hormones have been licensed for use in treating patients with type 2 diabetes. This study will assess whether there are defects in incretin hormones in a genetic type of diabetes called maturity onset diabetes of the young (MODY). It is not entirely clear why people with MODY have reduced insulin secretion and develop diabetes. This study will provide insights into whether defects in the incretin system are involved in the development of diabetes in MODY. The results could also indicate whether therapies that target the incretin hormones will have a role in MODY patients. This study emphasises the need to offer personalised care to patients with diabetes as those with different underlying causes of diabetes do not respond uniformly to treatments.