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Reference: Lewis, AJ, Miller, JJ, McCallum, C et al., (2016). Assessment of Metformin Induced Changes in Cardiac and Hepatic Redox State Using Hyperpolarized[1-13C]Pyruvate. Diabetes.Citable link to this page:

 

Assessment of Metformin Induced Changes in Cardiac and Hepatic Redox State Using Hyperpolarized[1-13C]Pyruvate.

Abstract: Metformin improves cardiovascular outcomes in type 2 diabetes, but its exact mechanisms of action remain controversial. We used hyperpolarized [1-(13)C]pyruvate magnetic resonance spectroscopy to determine the effects of metformin treatment upon heart and liver pyruvate metabolism in rats in vivo Both oral treatment for four weeks and a single intravenous metformin infusion significantly increased the cardiac [1-(13)C]lactate:[1-(13)C]pyruvate ratio, but had no effect on the [1-(13)C]bicarbonate + (13)CO2:[1-(13)C]pyruvate ratio, an index of pyruvate dehydrogenase flux. These changes were paralleled by a significant increase in the heart and liver cytosolic redox state, estimated from the [lactate]:[pyruvate] ratio, but not whole cell [NAD(+)]/[NADH] ratio. Hyperpolarized magnetic resonance imaging localised the increase in cardiac lactate to the left ventricular myocardium, implying a direct myocardial effect, though metformin had no effect on systolic or diastolic cardiac function. These findings demonstrate the ability of hyperpolarized pyruvate magnetic resonance spectroscopy to detect metformin induced changes in cytosolic redox biology, suggest that metformin has a previously unrecognised effect upon cardiac redox state and help to refine the design of impending hyperpolarized magnetic resonance studies in humans.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Accepted manuscriptDate of acceptance:2016-08-19Notes:© 2016 by the American Diabetes Association. This is the accepted manuscript version of the article. The final version is available online from the American Diabetes Association at: [10.2337/db16-0804].

Bibliographic Details

Publisher: American Diabetes Association

Publisher Website: http://www.diabetes.org/

Journal: Diabetessee more from them

Publication Website: http://diabetes.diabetesjournals.org/

Issue Date: 2016-08-25Identifiers

Doi: https://doi.org/10.2337/db16-0804

Eissn: 1939-327X

Issn: 0012-1797

Uuid: uuid:55cee995-e6c0-46c8-8c61-dfb03c6f540f

Urn: uri:55cee995-e6c0-46c8-8c61-dfb03c6f540f

Pubs-id: pubs:640785 Item Description

Type: journal-article;

Language: ENG

Version: Accepted manuscriptKeywords: JOURNAL ARTICLE

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Author: Lewis, AJ - Oxford, MSD, Physiology Anatomy and Genetics Oxford, MSD, RDM - - - Miller, JJ - Oxford, MSD, Physiology Anatomy and

Source: https://ora.ox.ac.uk/objects/uuid:55cee995-e6c0-46c8-8c61-dfb03c6f540f



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