Redox state and altered pyruvate metabolism contribute to a dose-dependent metformin-induced lactate production of human myotubes

Author:

Maurer Jennifer1,Zhao Xinjie2,Irmler Martin3,Gudiksen Anders4ORCID,Pilmark Nanna S.5,Li Qi2,Goj Thomas1,Beckers Johannes367ORCID,Hrabě de Angelis Martin367ORCID,Birkenfeld Andreas L.689,Peter Andreas168ORCID,Lehmann Rainer168ORCID,Pilegaard Henriette4,Karstoft Kristian510ORCID,Xu Guowang2ORCID,Weigert Cora168ORCID

Affiliation:

1. Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, Tübingen, Germany

2. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian, China

3. Institute of Experimental Genetics, Helmholtz Munich, Neuherberg, Germany

4. Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark

5. Centre for Physical Activity Research (CFAS), Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

6. German Center for Diabetes Research (DZD), Neuherberg, Germany

7. Chair of Experimental Genetics, Technical University of Munich, Freising, Germany

8. Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich, University of Tübingen, Tübingen, Germany

9. Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany

10. Department of Clinical Pharmacology, Bispebjerg and Fredriksberg Hospital, University Hospital of Copenhagen, Copenhagen, Denmark

Abstract

Metformin shifts the equilibrium of lactate dehydrogenase (LDH) reaction by low dose-induced phosphorylation of pyruvate dehydrogenase (PDH) resulting in inhibition of pyruvate oxidation and high dose-induced increase in NADH, which explains the dose-dependent lactate production of differentiated human skeletal muscle cells.

Funder

Mobility Programme of the Sino-German Center for Research Promotion

Key Foundation from the National Science Foundation of China

Research Foundation of Rigshospitalet

King Christian X Foundation

Bundesministerium für Bildung und Forschung

Aase og Ejnar Danielsens Fond

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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