The role of the neuregulins and their receptors in the islets of Langerhans

Signalling between cells within multi-cellular organisms is vital for coordination of processes such as cell division. Membrane receptors are important mediators of this signalling and one example are the receptor tyrosine kinases (RTKs). The RTKs can be divided into subfamilies, such as the epidermal growth factor receptor (EGFR) family. This family has an array of specific ligands called epidermal growth factors (EGFs). The neuregulins represent a sub-family of epidermal growth factors and are proteins which function in inter-cellular signalling that play a role in a number of organ systems, as well as a number of disease states in humans. Since they were first discovered, there has been rapid development in our knowledge of the neuregulins, but gaps are still present. This research project aims to further develop our knowledge through investigating the role of the neuregulins and their receptors in a model system, the islets of Langerhans in the pancreas. The expression pattern of all eleven EGF ligands (including the neuregulins) and their receptors in rat pancreatic islets, was determined using immunohistochemical techniques with specific antibodies. Immunofluorescence was then employed to look at the eo-localisation of ligandslreceptors with pancreatic hormones, in order to accurately describe the distribution ofligands/receptors within the model system's various cell types. The effect of re- folded neuregulins on CRI-G 1 (a rat insulinoma cell line ) cell proliferation, insulin secretion, and cell motility were investigated, with neuregulin NRG-3 found to have the greatest stimulatory effect on cell proliferation, NRG-4 the greatest stimulatory effect on insulin secretion, and NRG-l p the greatest stimulatory effect on rearrangement of the cell cytoskeleton. The information obtained in this work could prove to be clinically significant by aiding the treatment of type-l and type-2 diabetes, as well as islet cell cancer.EThOS - Electronic Theses Online ServiceGBUnited Kingdo