Astrid Hauge Evans

• Inter-cellular communication and the regulation of pancreatic islet function

Inter-cellular communication and the regulation of pancreatic islet function

Insulin-secreting beta-cells are located within the three-dimensional structure of the islet. Studies have shown that the secretory response of beta-cells located within these cell clusters is much improved compared to that of isolated beta-cells suggesting that interactions between islet cells are important for the regulation of beta-cell function. Islets are composite structures which also contain non-beta-cells such as glucagon-secreting alpha-cells and somatostatin-secreting delta-cells and communication between islet cells can therefore be both homotypic and heterotypic.

My research focuses on how interactions between islet cells may regulate insulin secretion and beta-cell survival, because both of these factors are important when developing new treatments for Type 2 diabetes, and for improving the outcome of islet transplantation therapy of Type 1 diabetes. To assess communication between islet cells and the importance of islet composition and architecture, a combination of in vitro models is used, including rodent and human primary islets and MIN6 pseudoislets combined with other islet cell lines. This work includes genomic analysis of MIN6 pseudoislets to identify novel elements involved in maintaining islet architecture and function as well as studies focussing on the effect of pseudoislet formation on beta-cell proliferation/apoptosis.

Beta-cell function may be affected heterotypically by hormones released from non-beta-cells. I am particularly interested in the role of delta-cell somatostatin (SST) and have used a SST knock-out mouse model developed by Low et al (J Clin Invest 107:1571-1580, 2001) to assess how delta-cell SST modulates islet hormone release. Our studies suggest a tonic inhibitory effect of SST on both insulin and glucagon secretion and these studies are being further expanded in collaboration Professor Peter Jones.

The importance of neuronal regulation of islet hormone release is another interest of mine. The neurotransmitter acetylcholine binds to muscarinic M3 receptors on the beta cells to enhance glucose-induced insulin secretion and I am currently investigating whether exposure to hyperglycaemia modulates M3 receptor expression and cholinergic activation of the islets.