, Volume 61, Issue 2, pp 445–454 | Cite as

Acute renal metabolic effect of metformin assessed with hyperpolarised MRI in rats

  • Haiyun Qi
  • Per M. Nielsen
  • Marie Schroeder
  • Lotte B. Bertelsen
  • Fredrik Palm
  • Christoffer Laustsen



Metformin inhibits hepatic mitochondrial glycerol phosphate dehydrogenase, thereby increasing cytosolic lactate and suppressing gluconeogenesis flux in the liver. This inhibition alters cytosolic and mitochondrial reduction–oxidation (redox) potential, which has been reported to protect organ function in several disease states including diabetes. In this study, we investigated the acute metabolic and functional changes induced by metformin in the kidneys of both healthy and insulinopenic Wistar rats used as a model of diabetes.


Diabetes was induced by intravenous injection of streptozotocin, and kidney metabolism in healthy and diabetic animals was investigated 4 weeks thereafter using hyperpolarised 13C-MRI, Clark-type electrodes and biochemical analysis.


Metformin increased renal blood flow, but did not change total kidney oxygen consumption. In healthy rat kidneys, metformin increased [1-13C]lactate production and reduced mitochondrial [1-13C]pyruvate oxidation (decreased the 13C-bicarbonate/[1-13C]pyruvate ratio) within 30 min of administration. Corresponding alterations to indices of mitochondrial, cytosolic and whole-cell redox potential were observed. Pyruvate oxidation was maintained in the diabetic rats, suggesting that the diabetic state abrogates metabolic reprogramming caused by metformin.


This study demonstrates that metformin-induced acute metabolic alterations in healthy kidneys favoured anaerobic metabolism at the expense of aerobic metabolism. The results suggest that metformin directly alters the renal redox state, with elevated renal cytosolic redox states as well as decreased mitochondrial redox state. These findings suggest redox biology as a novel target to eliminate the renal complications associated with metformin treatment in individuals with impaired renal function.


Diabetes Hyperpolarised MRI Metformin Renal function Renal metabolism Renal redox 



AMP-activated protein kinase


Lactate dehydrogenase


Mean arterial pressure


Mitochondrial glycerophosphate dehydrogenase


Pyruvate dehydrogenase


Oxygen tension


Oxygen consumption


Renal blood flow


Renal vascular resistance




Tubular Na+ reabsorption



The technical support of H. Vestergaard Nielsen (MR Research Centre, Department of Clinical Medicine, Aarhus University) and A. Fasching (Department of Medical Cell Biology, Uppsala University) are gratefully acknowledged.

Data availability

Data is available on request. Correspondence and requests for materials should be addressed to C Lautsen (cl@clin.au.dk).


The study was supported by the Sundhed og Sygdom, Det Frie Forskningsråd, Aarhus University research fund.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

HQ wrote the manuscript and contributed to acquisition and analysis of data. PMN and LBB contributed to acquisition of data and revised the manuscript. MS contributed to the acquisition of data, revised the manuscript and contributed to discussion. FP and CL conceived and designed the study, contributed to the analysis and interpretation of data, contributed to discussion, and wrote and reviewed the manuscript. All authors approved the final version to be published. CL is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Supplementary material

125_2017_4445_MOESM1_ESM.pdf (550 kb)
ESM (PDF 549 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.MR Research Centre, Department of Clinical MedicineAarhus UniversityAarhus NDenmark
  2. 2.Department of Medical Cell BiologyUppsala UniversityUppsalaSweden

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