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Property "Has-20abstract" (as page type) with input value "-5B-5BImage:MITOEAGLE-2Dlogo.jpg-7Cleft-7C100px-7Clink=http:-2F-2Fwww.mitoglobal.org-2Findex.php-2FMITOEAGLE-7CCOST-20Action-20MitoEAGLE-5D-5D-0AMetformin-20is-20an-20antidiabetic-20drug-20that-20exerts-20its-20effects-20by-20inhibition-20of-20hepatic-20gluconeogenesis-20and-20upregulation-20of-20glucose-20uptake-20in-20peripheral-20tissues,-20such-20as-20skeletal-20muscle.-20Despite-20being-20used-20in-20clinical-20practice-20for-20over-2060-20years,-20its-20cellular-20mechanisms-20of-20action-20and-20molecular-20targets-20have-20not-20been-20elucidated-20yet.-20Proposed-20mechanisms-20of-20action-20are-20activation-20of-20AMPK-20and-20inhibition-20of-20complex-20I-20of-20the-20respiratory-20chain.-20Many-20-27-27in-20vitro-27-27-20studies-20claim-20that-20metformin-20inhibits-20complex-20I,-20but-20the-20concentrations-20used-20in-20these-20studies-20are-20usually-20a-20lot-20higher-20than-20the-20plasma-20concentrations-20in-20patients-20taking-20the-20drug-20orally.-20-5B1-5D-20The-20aim-20of-20our-20research-20was-20to-20explore-20the-20effects-20of-20therapeutic-20metformin-20concentration-20on-20cell-20viability-20and-20mitochondrial-20respiration-20of-20C2C12-20cells.-0A-0AC2C12-20mouse-20myoblast-20cell-20line-20was-20treated-20with-20a-20wide-20range-20of-20metformin-20concentrations-20(3-2D12800-20µM)-20for-20cell-20viability-20assays,-20and-20with-20two-20different-20metformin-20concentrations-20(50-20µM-20and-205-20mM)-20for-20measuring-20mitochondrial-20respiration.-20Cell-20viability-20was-20measured-20by-20crystal-20violet-20and-20acid-20phospatase-20assays,-20and-20mitochondrial-20respiration-20by-20high-20resolution-20respirometry,-20with-20Oroboros-20O2k.-0A-0AMetformin-20treatment-20did-20not-20cause-20a-20decrease-20in-20cell-20viability-20in-20the-20micromolar-20range-20(3-2D800-20µM),-20but-20milimolar-20concentrations-20(3-20and-2013-20mM)-20-20caused-20a-20significant-20decrease-20in-20cell-20viability.-20Respirometric-20analysis-20showed-20that-205-20mM-20metformin-20caused-20a-20decrease-20in-20ROUTINE-20and-20OXPHOSCI,-20while-20OXPHOSCII-20was-20unaltered,-20both-20with-20long-20(24-20h)-20and-20short-20(metformin-20titration-20directly-20in-20the-20chamber)-20treatment.-20On-20the-20contratry,-2050-20µM-20treatment-20caused-20a-20slight-20increase-20in-20ROUTINE,-20OXPHOSCI-20and-20OXPHOSCII-20when-20cells-20are-20treated-20with-20metformin-20for-2024-20h,-20but-20there-20is-20no-20change-20in-20any-20of-20the-20respiratory-20states-20when-20using-20the-20short-20treatment.-0A-0AAccording-20to-20these-20results-20metformin-20concentration-20that-20has-20been-20found-20to-20cause-20complex-20I-20inhibition-20(5-20mM)-20is-20cytotoxic-20to-20muscle-20cells.-20The-20concentration-20that-20is-20comparable-20to-20that-20found-20-27-27in-20vivo-27-27-20(50-20µM)-20is-20not-20cytotoxic-20to-20C2C12-20cells-20and-20does-20not-20cause-20inhibition-20of-20complex-20I-20activity.-20Thus,-20this-20raises-20the-20question-20if-20the-20therapeutic-20effects-20of-20metformin-20can-20be-20ascribed-20to-20complex-20I-20inhibition-20-27-27in-20vivo-27-27." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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