Investigation into the role of dicarbonyl and osmotic stress in hepatic complications of diabetes

With the increase in incidence of diabetes, mainly Type 2 diabetes, in the worldwide population, understanding the underlying pathology of its complications will provide invaluable information to develop effective adjuvant therapies.

This project specifically focuses on the hepatic complications of Type 2 diabetes and the role played by hyperglycaemia, both metabolites and its osmotic action.  There is a significant lack of knowledge of how hyperglycaemia affects hepatocytes to increase the incidence of hepatic disease and how this may be therapeutically countered, this project aims to rectify this deficit.  The glucose metabolite methylglyoxal has been identified as being a key mediator in diabetic complications of the vascular and renal systems, as well as being shown to have direct damaging effects on hepatocyte function.  However, the concentrations of exogenously applied methylglyoxal in vitro are far in excess of those found in diabetic plasma, possibly compromising the interpretation of the findings.  Development of a more physiological model to increase intracellular concentrations of methylglyoxal is essential to further understanding its cellular damaging effects.  Understanding the pathology underpinning the increased risk of hepatic disease in diabetics hence allows for development of therapeutic adjuvants, which if already approved for clinical use may be deployed in a much-reduced timescale.

I am a self-funded student and my supervisors at the University of Brighton are Dr Jon G Mabley and Dr Greg Scutt.