Autophagy is a process by which cells can relieve stress, by recycling damaged cellular machinery and disposing of misfolded and aggregated proteins. Autophagy can be a beneficial process for beta cell survival. We have been investigating C3, a protein that is highly expressed in human pancreatic islets. We found that pancreatic islets from human donors with diabetes produced higher levels of the C3 protein, than islets from diabetic patients. When we removed the C3 gene from beta cells grown in the lab, preventing them from producing the C3 protein, we found that autophagy no longer worked properly. These cells were therefore more vulnerable to cell death when faced with stress.

C3 is usually released from cells into the blood, but we have found that C3 exists within beta cells, where it interacts with an autophagy protein called ATG16L1. We are therefore investigating exactly how C3 exists inside cells, and how it regulates autophagy. This involves basic studies of cellular biology and increases our understanding of this otherwise well-studied protein. We are also developing new mouse models to investigate the specific role of C3 in beta cells during diabetes development, to assess the contribution of this protein to beta cell function and survival, with the hope that this will reveal new mechanisms that can be targeted by future therapeutics.