Lydia Le Page
Doctoral Student at the
Rex Richards Building, South Parks Road, Oxford OX1 3QU
I am carrying out my PhD in Dr Damian Tyler's research group, in the Department of Physiology, Anatomy and Genetics at the University of Oxford, co-supervised by Dr Edvin Johansson at AstraZeneca in Sweden. My work has investigated the pharmacological and physiological regulation of pyruvate dehydrogenase in diabetes, using magnetic resonance spectroscopy.
The main technique I have used allows us to assess metabolism in vivo. We use the novel technique of hyperpolarizing compounds, such as 13C-labelled pyruvate, and then inject them into anaesthetised animals in an MRI system. The hyperpolarization increases the signal we receive over 10,000-fold in comparison to the same compounds at thermal equilibrium. This means we can take a carbon spectrum every second, and watch as the pyruvate is metabolised, transferring its carbon-13 label into downstream metabolites. This gives an assessment of real-time carbohydrate metabolism, specifically of flux through pyruvate dehydrogenase.
I have applied this technique to a type II diabetic rat model. I have developed and validated a two-organ acquisition so we can assess cardiac and hepatic metabolism in one injection of hyperpolarized pyruvate. My subsequent work with this acquisition has assessed the effects of PDH stimulation with drug compounds and the effect of hypoxia, on cardiac and hepatic metabolism in the control and diabetic animal.
I presented my work at the 2014 ISMRM conference:'Pyruvate dehydrogenase activation normalises carbohydrate metabolism and diastolic function in the diabetic heart' and 'Real-time assessment of the effect of acute and chronic hypoxia on cardiac metabolism in the control and diabetic rat: an in vivo study'.
Both were oral presentations.