Assessment of Metformin induced changes in cardiac redox state using hyperpolarized[1-13C]pyruvate
© Lewis et al. 2016
Published: 27 January 2016
Metformin improves cardiovascular outcomes in diabetes, but its mechanism of action is controversial. Recent evidence suggests that Metformin reduces gluconeogenesis by altering hepatic redox state. Whether Metformin also alters cardiac redox state and metabolism is unknown, in part because of the difficulty in measuring cardiac metabolism in vivo. Hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy can assess the redox coupled interconversion of pyruvate and lactate with spatial localization to the heart. We therefore used hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy to investigate the effects of acute and chronic metformin treatment upon cardiac and hepatic metabolism.
In the first study, male Wistar rats (n = 10 per group) were given an intravenous infusion of either 50 mg Metformin or saline. Hyperpolarized [1-13C]pyruvate spectroscopy was performed 45 minutes later, with slice selective spectra acquired from two axial slabs covering the heart and liver using a 7T preclinical MR system and a volume 13C transmit / two-channel surface receive RF coil. We next tested the effects of longer term Metformin treatment (4 weeks) in both control rats and rats with a high-fat feeding and streptozotocin induced model of type II diabetes (n = 6-8 per group). We again used hyperpolarized [1-13C]pyruvate spectroscopy to assess cardiac and hepatic metabolism, and also performed echocardiography to assess cardiac diastolic function.
Both acute and chronic metformin treatment significantly increased the cardiac [1-13C]lactate:[1-13C]pyruvate ratio, likely reflecting a shift in cardiac redox state. These findings suggest that hyperpolarized 1-13C]pyruvate magnetic resonance spectroscopy is sensitive to Metformin induced changes in redox biology and can identify novel cardiac metabolic effects of this commonly prescribed drug.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.