Diabetes Research

Another problems with islet transplantation is that the side effects of the anti-rejection drugs (immunosuppression) outweigh the benefits of improved glucose control in most patients. Therefore, most patients are not suitable for islet transplantation therapy and therefore must rely on insulin injections to control their diabetes. Microencapsulation of islets may allow transplantation of islets in the absence of immunosuppression. The islets are encapsulated in alginate, a polysaccharide derived from seaweed. The alginate forms a network around the islets, which is tight enough to prevent immune cells from making contact with the islets and killing them. The alginate network is, however, open enough to allow the diffusion of nutrients into the capsule and insulin out from the capsule. Therefore this can allow transplantation in the absence of immunosuppression therapy.

The aim of the research is to understand the molecular basis and anatomical pathways involved in leptin and insulin action and the role of the immune system and inflammation in obesity and the metabolic syndrome using both in vitro and in vivo models.

Autoimmunity in Type 1 diabetes: Type 1 diabetes is the result of the destruction of insulin-secreting pancreatic beta cells by a process in which autoimmune recognition of beta cell proteins is implicated. My research group has long-standing interests in the identification and characterisation of beta cell targets of the autoimmune response in Type 1 diabetes, with the view of developing strategies to identify individuals at risk for disease, and to apply antigen specific immune intervention to prevent disease progression in high-risk subjects. My group was the first to detect circulating autoantibodies to a tyrosine phosphatase-like protein, IA-2, in diabetic patients, and this antibody marker is now widely used for the prediction and diagnosis of disease. We have subsequently identified a region of the IA-2 molecule that is very commonly recognised by both ciirculating autoantibodies and T-cells in Type 1 diabetes. We are currently investigating the relationships between T- and B-cell responses to this and other regions of the IA-2 molecule, and the potential for this region to form the basis of antigen-specific vaccination protocols to prevent disease.

Development and function of pancreatic beta cells: IA-2 is a tyrosine phosphatase-like protein localised to secretory granules of pancreatic beta cells, as well as to secretory vesicles of a number of other neuroendocrine organs, including the pituitary. Our recent studies have shown that IA-2 is an important regulator of beta cell secretory granule content and insulin secretion. IA-2 is poorly expressed in fetal life, but is up-regulated after birth, in parallel with increases in islet insulin secretion in response to glucose. We are currently interested in understanding the changes in beta cell gene expression that occur during the functional maturation of pancreatic beta cells during their development, and the influences of hormones and environmental factors, particularly diet, on the development and function of the endocrine pancreas. These studies will aid our understanding of how early exposure to environmental factors can influence susceptibility to Type 1 and Type 2 diabetes later in life.