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Abstract #0801

The acute effects of metformin on cardiac and hepatic metabolism: a hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy study

Andrew Lewis 1 , Chloe McCallum 1 , Jack Miller 1,2 , Lisa Heather 1 , and Damian J Tyler 1

1 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 2 Department of Physics, University of Oxford, Oxford, United Kingdom

The mechanism of action of metformin in type II diabetes is uncertain, but may involve altered cellular redox state and carbohydrate metabolism. We used hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy to investigate the acute effects of a metformin infusion upon cardiac and hepatic metabolism in Wistar rats (n=6-7 per group). An infusion of 50mg metformin increased the cardiac [1-13C]lactate to [1-13C]pyruvate ratio compared to a control infusion (P<0.05), without affecting pyruvate dehydrogenase flux. These findings suggest an increase in the size of the cardiac lactate pool and/or increased lactate dehydrogenase activity, demonstrating that metformin has previously unknown effects upon cardiac metabolism.

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